Role of cyclooxygenases 1 and 2 in the maintenance of colonic mucosal integrity in an experimental colitis model.

The role of cyclooxygenase (COXs) isoforms in maintaining colonic mucosal integrity is not fully understood. This study aimed to evaluate the role of COX-1 and -2 on colonic mucosal integrity in an experimental colitis model. Colitis was induced in Wistar rats by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (20 mg + 50% ethanol). The control group (sham group) received saline only. After 7, 14, or 28 days, colonic samples were removed, and macroscopic lesion scores, wet weight, myeloperoxidase activity, and transepithelial electrical resistance (TER) were determined. In other rat groups, colonic samples from the sham group and a 7th day post-colitis group were mounted in Üssing chambers with the luminal side exposed to a buffer solution (control), acetylsalicylic acid (ASA), SC-560 (COX-1 inhibitor), or celecoxib (COX-2 inhibitor). TER and epithelial permeability to fluorescein were measured. The 7th day colitis group had higher macroscopic damage scores, wet weight, and myeloperoxidase activity and lower basal TER than the sham, 14th day colitis, and 28th day colitis groups. Inhibition of COX-1 but not COX-2 significantly decreased TER and increased permeability to fluorescein in the 7th day post-colitis group compared to the sham group. Additionally, ASA decreased the colonic mucosal integrity on day seven post-colitis compared to the sham group. A decrease in the colonic mucosa integrity in the experimental colitis model can be aggravated only by the inhibition of COX-1, which demonstrated the importance of this enzyme in the maintenance of colonic mucosal integrity.

Lower low density lipoprotein cholesterol associates to higher mortality in non-diabetic heart failure patients.

Background: In patients with established heart failure (HF) low total cholesterol levels associate with worse prognosis. Evidence concerning the impact of Low-density lipoprotein cholesterol (LDL-c) in HF is scarce. We aimed to evaluate the prognostic impact of LDL-c in patients with HF, both with and without diabetes mellitus (DM). Methods: We retrospectively analyzed outpatients with chronic HF with systolic dysfunction followed in our HF clinic from January/2012 to May/2018. LDL-c was calculated using the Friedewald's formula. Patients without a complete lipid profile were excluded. The endpoint under analysis was all-cause mortality. Patients were followed until January/2021. A Cox-regression analysis was used to study the prognostic impact of LDL-c. The LDL-c cut-off used was 100 mg/dL (mean value). Analysis was stratified according to the coexistence of DM. Multivariate models were built adjusting for age, sex, coronary artery disease, atherosclerotic non-coronary artery disease, arterial hypertension, smoking status, statin use, severity of systolic dysfunction, creatinine clearance and evidence-based therapy. Results: We studied 522 chronic HF patients, mean age was 70 years, 66.5% males. Severe systolic dysfunction was present in 42.7%, 30.5% had coronary heart disease, 60.5% had arterial hypertension, 41.6% had DM. A total of 92.0% were treated with beta blocker, 87.5% with an ACEi/ARB and 29.1% with a MRA. During a median follow-up of 53 (interquartile range 33-73) months, 235 (45%) patients died. Patients with LDL-c ≤100 mg/dL presented increased multivariate-adjusted risk of all-cause mortality: HR = 1.58 (95% CI: 1.08-2.30), p = 0.02. When patients were stratified according to DM, LDL-c ≤100 mg/dL was independently associated with increased death risk - HR = 1.55 (95% CI:1.05-2.30), p = 0.03 in patients without DM; in patients with DM no association was detected - multivariate-adjusted HR = 1.18 (95% CI: 0.77-1.80), p = 0.44. Conclusion: Non-DM HF patients with LDL-c>100 mg/dL have a 35% reduction in the mortality risk when compared with those with lower values. The "cholesterol paradox" in HF also applies to LDL-c in non-DM patients.

The effect of TB patient delay on loss to follow-up in Portugal.

BACKGROUND: Early identification of TB cases, followed by treatment to completion, are essential for controlling and preventing the disease. Previous studies have found some factors associated with both loss to follow-up (LTFU) and patient delay. We aim to build a causal model to investigate the association between TB patient delay and LTFU.METHODS: Pulmonary TB cases were identified using the national surveillance system in Portugal between 2008 and 2017. A directed acyclic graph was used to identify the minimal set of variables to adjust for when studying the association between delay (exposure) and LTFU (outcome). Crude and adjusted hazard were estimated using Cox regression.RESULTS: Nearly 4% of the patients did not follow up treatment. There was no association between patient delay and LTFU, even after adjustment with the minimal set of covariates. Factors associated with a higher risk of LTFU were being younger, being unemployed, living in urban areas, having HIV and the abuse of alcohol and drugs.CONCLUSION: Patient delay was not associated with LTFU, while social conditions were. Future research should investigate the underlying reasons why patients discontinue TB treatment and use these findings to develop targeted interventions that can support patients in completing their treatment regimen.

Structural characterization of the Aspergillus niger citrate transporter CexA uncovers the role of key residues S75, R192 and Q196.

The Aspergillus niger CexA transporter belongs to the DHA1 (Drug-H+ antiporter) family. CexA homologs are exclusively found in eukaryotic genomes, and CexA is the sole citrate exporter to have been functionally characterized in this family so far. In the present work, we expressed CexA in Saccharomyces cerevisiae, demonstrating its ability to bind isocitric acid, and import citrate at pH 5.5 with low affinity. Citrate uptake was independent of the proton motive force and compatible with a facilitated diffusion mechanism. To unravel the structural features of this transporter, we then targeted 21 CexA residues for site-directed mutagenesis. Residues were identified by a combination of amino acid residue conservation among the DHA1 family, 3D structure prediction, and substrate molecular docking analysis. S. cerevisiae cells expressing this library of CexA mutant alleles were evaluated for their capacity to grow on carboxylic acid-containing media and transport of radiolabeled citrate. We also determined protein subcellular localization by GFP tagging, with seven amino acid substitutions affecting CexA protein expression at the plasma membrane. The substitutions P200A, Y307A, S315A, and R461A displayed loss-of-function phenotypes. The majority of the substitutions affected citrate binding and translocation. The S75 residue had no impact on citrate export but affected its import, as the substitution for alanine increased the affinity of the transporter for citrate. Conversely, expression of CexA mutant alleles in the Yarrowia lipolytica cex1Δ strain revealed the involvement of R192 and Q196 residues in citrate export. Globally, we uncovered a set of relevant amino acid residues involved in CexA expression, export capacity and import affinity.

The compound event that triggered the destructive fires of October 2017 in Portugal.

Portugal is regularly affected by destructive wildfires that have severe social, economic, and ecological impacts. The total burnt area in 2017 (∼540,000 ha) marked the all-time record value since 1980 with a tragic toll of 114 fatalities that occurred in June and October events. The local insurance sector declared it was the costliest natural disaster in Portugal with payouts exceeding USD295 million. Here, the 2017 October event, responsible for more than 200,000 ha of burnt area and 50 fatalities is analyzed from a compound perspective. A prolonged drought led to preconditioned cumulative hydric stress of vegetation in October 2017. In addition, on 15 October 2017, two other major drivers played a critical role: 1) the passage of hurricane Ophelia off the Coast of Portugal, responsible for exceptional meteorological conditions and 2) the human agent, responsible for an extremely elevated number of negligent ignitions. This disastrous combination of natural and anthropogenic drivers led to the uncontrolled wildfires observed on 15 October.

Attention deficit hyperactivity disorder and restless leg syndrome across the lifespan: A systematic review and meta-analysis.

This systematic review aims to assess the association between attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for original articles that reported prevalence data on ADHD and RLS until January 24th, 2023. Two independent reviewers evaluated the quality of the articles using the National Institutes of Health assessment tool. Among the 208 articles identified between 1996 and 2022, 29 were included. In large general population studies, 2.6-15.3% of participants met the RLS criteria, of which 3.2-17.4% presented with ADHD. In the ADHD group, RLS symptoms ranged from 11 to 42.9% in children and 20-33.0% in adults. This suggests a strong co-occurrence between RLS and ADHD. A common characteristic of these conditions is sleep fragmentation, as discussed in the reviewed papers. Although large-scale studies with comparable diagnostic criteria across the lifespan are required, our findings may advocate a possible common physiological pathway, including sleep fragmentation and dopaminergic system impairment.

Vitamin D levels in Portuguese military personnel.

INTRODUCTION: In Portugal, most adults have inadequate levels of vitamin D. Active duty military personnel need to be always ready for duty, perform tasks in specific contexts and overcome high physical and mental demands, which raises the relevance of knowing their vitamin D levels. This study aims to characterise vitamin D levels of Portuguese active duty military personnel and evaluate the effect of military status on the prevalence of vitamin D sufficiency, adjusted for season of the year, age and gender. METHODS: A retrospective cross-sectional study, based on vitamin D measurements carried out at the Armed Forces Hospital between 2014 and 2020, was fulfilled including the variables age, gender, vitamin D level and dosing date for military personnel and civilians. Comparison of proportions test and the generalised linear regression model were used for data analysis with a significance level of 5%. RESULTS: Out of 2782 subjects, 62.7% were military personnel. Mean±SD level of vitamin D was 24.5±10.6 ng/mL and 23.7±11.5 ng/mL in military personnel and civilians, respectively. In the military personnel, the prevalence of vitamin D sufficiency, insufficiency and deficiency was, respectively, 25.2%, 40.1% and 34.6%. Prevalence of vitamin D sufficiency was similar in the civilians cohort and, also, between Armed Forces branches. Military status had no effect on the prevalence of vitamin D sufficiency, especially after adjustments. CONCLUSIONS: We present data on vitamin D levels of Portuguese active duty military personnel. Our results found that military personnel are no more at risk of vitamin D inadequacy than civilians, but only a quarter of active duty military personnel had vitamin D sufficiency. Therefore, they can benefit from vitamin D levels assessment towards vitamin D levels optimisation. Further studies are still needed, especially among military personnel with higher risk of vitamin D deficiency.

Role of cyclooxygenases 1 and 2 in the maintenance of colonic mucosal integrity in an experimental colitis model

The role of cyclooxygenase (COXs) isoforms in maintaining colonic mucosal integrity is not fully understood. This study aimed to evaluate the role of COX-1 and -2 on colonic mucosal integrity in an experimental colitis model. Colitis was induced in Wistar rats by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (20 mg + 50% ethanol). The control group (sham group) received saline only. After 7, 14, or 28 days, colonic samples were removed, and macroscopic lesion scores, wet weight, myeloperoxidase activity, and transepithelial electrical resistance (TER) were determined. In other rat groups, colonic samples from the sham group and a 7th day post-colitis group were mounted in Üssing chambers with the luminal side exposed to a buffer solution (control), acetylsalicylic acid (ASA), SC-560 (COX-1 inhibitor), or celecoxib (COX-2 inhibitor). TER and epithelial permeability to fluorescein were measured. The 7th day colitis group had higher macroscopic damage scores, wet weight, and myeloperoxidase activity and lower basal TER than the sham, 14th day colitis, and 28th day colitis groups. Inhibition of COX-1 but not COX-2 significantly decreased TER and increased permeability to fluorescein in the 7th day post-colitis group compared to the sham group. Additionally, ASA decreased the colonic mucosal integrity on day seven post-colitis compared to the sham group. A decrease in the colonic mucosa integrity in the experimental colitis model can be aggravated only by the inhibition of COX-1, which demonstrated the importance of this enzyme in the maintenance of colonic mucosal integrity.

Non-adherence to COVID-19 lockdown: who are they? A cross-sectional study in Portugal.

OBJECTIVES: The SARS-CoV-2 virus has spread worldwide, leading governments to implement mitigation measures. Understanding the reluctance to adhere to non-pharmacological interventions might help promote adherence to these measures. This study aimed to identify factors associated with non-adherence to the first lockdown in Portugal. STUDY DESIGN: Cross-sectional study. METHODS: This study used data from a Portuguese community-based survey entitled 'COVID-19 Barometer: Social Opinion'. Data were collected on risk perception, health status and social experiences using a snowball sampling technique. The event of interest corresponded to participants who reported not staying home during the lockdown period, serving as a proxy for non-adherence to lockdown. Logistic regression was used to identify factors associated with non-adherence to the first lockdown. RESULTS: Responses from 133,601 individual questionnaires that were completed during the first week of the first lockdown in 2020 were analysed. A minority of participants (5.6%) reported non-adherence to lockdown (i.e. leaving home for reasons other than essential situations). Working in the workplace was the factor with the strongest association of non-adherence to the lockdown. Several other factors were also associated with non-adherence to the first lockdown; namely, being a man, being a student, having a low level of education, having a low income, living alone or with a high-infection-risk professional (e.g. doctor, nurse, pharmaceutical, health technician, firefighter, police officer, military, essential services worker), perceiving the risk of getting COVID-19 to be high, not having social support in case of infection, feeling agitated, sad or anxious every day, and considering the preventive measures to be unimportant or inadequate. CONCLUSIONS: Non-adherence to lockdown was associated with socio-economic, trust and perception factors. Future research should investigate the mechanisms underlying these associations to help identify the population groups who are most at risk of non-adherence.

Ecological factors associated with areas of high tuberculosis diagnosis delay.

OBJECTIVE: We aimed to identify areas of high tuberculosis (TB) diagnosis delay in mainland Portugal in 2017 and ecological factors associated with these areas. STUDY DESIGN: This was an ecological study. METHODS: We considered all notified pulmonary TB cases from the Portuguese National Tuberculosis Surveillance System in mainland Portugal. Diagnostic delays were calculated at the municipality level. Demographic variables, proxies for TB awareness, health services capacity indicators, and socio-economic variables were included and extracted from official databases, such as Statistics Portugal, Ministeries, Foreigners and Border Services. We used spatial analysis to identify areas of high delay in 2017 and logistic generalised additive models to identify ecological factors associated with the identified cluster. RESULTS: We identified an area of high delay in 2017 in the South region of the country. Overall, municipalities with a smaller population density, smaller proportion of unemployed, fewer health centres and higher old-age dependency ratio, proportion of men, TB incidence, proportion of immigrants and high school dropout had a higher probability of belonging in a high delay area. CONCLUSION: The role of primary health care in TB diagnosis should be further explored. Interventions should address factors interplaying at the local and individual levels. Policies influencing social and health conditions, leading to changes in individual behaviour, can lead to sustained improvements over time.

Evaluation of miRNAs regulation of BDNF and IGF1 genes in T2DM insulin resistance in experimental models: bioinformatics based approach.

microRNAs (miRNAs) are recognized as diabetes mellitus type 2 (T2DM) biomarkers useful for disease metabolism comprehension and have great potential as therapeutics targets. BDNF and IGF1 increased expression are highly involved in the benefits of insulin and glucose paths, however, they are down-regulated in insulin resistance conditions, while their expression increase is correlated to the improvement of glucose and insulin metabolism. Studies suggest the microRNA regulation of these genes in several different contexts, providing a novel investigation approach for comprehending T2DM metabolism and revealing potential therapeutic targets. In the present study, we investigate in different animal models (human, rat, and mouse) miRNAs that target BDNF and IGF1 in skeletal muscle tissue with T2DM physiological conditions. Bioinformatics tools and databases were used to miRNA prediction, molecular homology, experimental validation of interactions, expression in the studied physiological condition, and network interaction. The findings showed three miRNAs candidates for IGF1(miR-29a, miR-29b, and miR-29c) and one for BDNF (miR-206). The experimental evaluations and the search for the expression in skeletal muscle from T2DM subjects confirmed the predicted interaction between miRNA-mRNA for miR-29b and miR-206 through human, rat, and mouse models. This interaction was reaffirmed in multiple network analyses. In conclusion, our results show the regulation relationship between miR-29b and miR-206 with the investigated genes, in several tissues, suggesting an inhibition pattern. Nevertheless, these data show a large number of possible interaction physiological processes, for future biotechnological prospects.

Rich but random: parasite communities of snouted treefrog, Scinax fuscovarius (Anura: Hylidae), in Bodoquena Mountains, western Brazil.

Hosts represent discrete habitats that contain finite parasite communities, and individual hosts can be used as replicates in parasitism studies, such as investigations of the processes that mediate the formation of parasite communities. However, within a single host population, there may be singularities among individuals that affect parasite contact rates. Accordingly, the goals of the present study were to document the parasites associated with the small treefrog Scinax fuscovarius, to verify possible variation and co-occurrences in parasite infracommunities, and to assess the effects of host characteristics (size and sex) on infracommunity structure. Treefrog specimens (n = 75) were collected from the Bodoquena Mountains in Mato Grosso do Sul, Brazil. After collection, the specimens were transported to the laboratory, and examined for parasitic. The parasites found were removed, fixed, and identified. Patterns in parasite infracommunity organization were analyzed using the checkerboard score index, which was calculated using a presence-absence matrix. The matrix was randomized under the null hypothesis that the infracommunities independently represent the component community. Forty-two (56%) of the individuals harbored at least one parasite, and a total of 500 metazoan parasites were recovered, with a particularly rich composite community of 18 taxa, including 13 nematodes, two trematodes, one cestode, one oligochaete, and one mite larvae. The parasite species were randomly distributed among the infracommunities, with no evidence of co-occurrence, segregation, or aggregation. However, both body size and sex influenced infection, with larger hosts harboring more parasites and parasites were more abundant in male specimens and more species rich in female specimens. These results suggest that the parasite infracommunities of S. fuscovarius are shaped by both random factors and individual host characteristics.

Changes in gut-brain axis parameters in adult rats of both sexes with different feeding pattern that were early nicotine-exposed.

Nicotine is an endocrine disruptor and imprinting factor during breastfeeding that can cause food intake imbalance in the adulthood. As nicotine affects the intestinal microbiota, altering the composition of the bacterial communities and short-chain fatty acids (SCFAs) synthesis in a sex-dependent manner, we hypothesized that nicotine could program the gut-brain axis, consequently modifying the eating pattern of adult male and female rats in a model of maternal nicotine exposure (MNE) during breastfeeding. Lactating Wistar rat dams received minipumps that release 6 mg/kg/day of nicotine (MNE group) or saline for 14 days. The progeny received standard diet from weaning until euthanasia (26 weeks of age). We measured: in vivo electrical activity of the vagus nerve; c-Fos expression in the nucleus tractus solitarius, gastrointestinal peptides receptors, intestinal brain-derived neurotrophic factor (BDNF), SCFAs and microbiota. MNE females showed hyperphagia despite normal adiposity, while MNE males had unchanged food intake, despite obesity. Adult MNE offspring showed decreased Bacteroidetes and increased Firmicutes, Actinobacteria and Proteobacteria. MNE females had lower fecal acetate while MNE males showed higher vagus nerve activity. In summary nicotine exposure through the milk induces long-term intestinal dysbiosis, which may affect eating patterns of adult offspring in a sex-dependent manner.

Patient and healthcare delays in critical and non-critical pulmonary tuberculosis incidence areas in Portugal: are there differences?

OBJECTIVES: To characterize patient, healthcare, and total delay in diagnosing pulmonary tuberculosis (PTB) in critical (higher PTB incidence) and non-critical (lower PTB incidence) areas and their determinants considering clinical and sociodemographic factors. STUDY DESIGN: Retrospective cohort study. METHODS: Data was retrieved from the Portuguese National Tuberculosis Surveillance System (SVIG-TB). Were included in the study all active PTB patients (n = 11,762) notified between 2008 and 2017. Spatial analysis was used to define critical and non-critical areas. Kaplan-Meier estimator, logrank test, and Cox regression were conducted, stratified by area. RESULTS: PTB cases in critical areas (n = 6594, 56.1%) presented longer patient median delay (41 vs 31days), shorter healthcare median delay (7 vs 10 days), and longer total median delay (63 vs 61days) t.han non-critical areas. Patient and total delay increased in both areas over time, while healthcare delay only increased in non-critical areas. Icn both areas, being from a high TB incidence country and alcohol abuse were associated with longer patient delays. Being female, older age, and oncologic diseases were associated with longer healthcare delays. Respiratory diseases were only associated with a longer healthcare delay in non-critical areas. Being female, older, and from a high TB incidence country were associated with a longer total delay in both areas. CONCLUSIONS: Patient delay was significantly longer in critical areas, and healthcare delay was significantly longer in non-critical areas. Several factors associated with longer delays have been identified, most of which are shared by critical and non-critical areas. Differences in patient and healthcare delay, for example, by sex, age, or country of birth, highlight the need for targeted public health interventions to help reduce these differences.

Effects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study.

BACKGROUND: Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant. METHODS: Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24-51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed. RESULTS: BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2). CONCLUSION: BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.

First report of root-knot nematode, Meloidogyne incognita, infecting hops, Humulus lupulus, in São Paulo, Brazil.

In 2019, during a nematologic survey in Jaboticabal, Brazil, root-knot nematode Meloidogyne incognita parasitizing hops (Humulus lupulus) was identified with based on morphological characters of adults, esterase phenotypes (n = 16), and molecular analysis. Modified Koch's postulates was carried out and after 90 days, the average total population recovered had different stages of development, with a reproductive factor (RF) of 4.81. This is the first report of H. lupulus as a host of M. incognita in the state of São Paulo and in Brazil.

Detection and Imaging of Damages and Defects in Fibre-Reinforced Composites by Magnetic Resonance Technique.

Defectively manufactured and deliberately damaged composite laminates fabricated with different continuous reinforcing fibres (respectively, carbon and glass) and polymer matrices (respectively, thermoset and thermoplastic) were inspected in magnetic resonance imaging equipment. Two pulse sequences were evaluated during non-destructive examination conducted in saline solution-immersed samples to simulate load-bearing orthopaedic implants permanently in contact with biofluids. The orientation, positioning, shape, and especially the size of translaminar and delamination fractures were determined according to stringent structural assessment criteria. The spatial distribution, shape, and contours of water-filled voids were sufficiently delineated to infer the amount of absorbed water if thinner image slices than this study were used. The surface texture of composite specimens featuring roughness, waviness, indentation, crushing, and scratches was outlined, with fortuitous artefacts not impairing the image quality and interpretation. Low electromagnetic shielding glass fibres delivered the highest, while electrically conductive carbon fibres produced the poorest quality images, particularly when blended with thermoplastic polymer, though reliable image interpretation was still attainable.

Correlation of molecular data with histopathological and clinical features in a series of 66 patients with medullary thyroid carcinoma.

PURPOSE: Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC. METHODS: The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics. RESULTS: Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome. CONCLUSION: Our results support the idea that a genotype-phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.

Nicotine exposure during lactation causes disruption of hedonic eating behavior and alters dopaminergic system in adult female rats.

Tobacco smoke during gestation is associated with increased consumption of palatable foods by the offspring in humans and rats. Postpartum relapse is observed in lactating women who quit smoking during pregnancy, putting their children at risk of adverse health outcomes caused by secondhand smoke. Nicotine is transferred through milk and alters the dopaminergic reward system of adult male rats, reducing dopamine action in the nucleus accumbens (NAc) and hypothalamic arcuate nucleus. Here, we evaluated the long-term effects of nicotine-only exposure during lactation on eating behavior, anxiety, locomotion, dopaminergic system, hypothalamic leptin signaling and nicotinic receptor in the adult female rat progeny. Two days after birth (PN2), Wistar rat dams were separated into control and nicotine (Nic) groups for implantation of osmotic minipumps that released respectively saline or 6 mg/kg nicotine. Lactating dams were kept with 6 pups. After weaning (PN21; nicotine withdrawal), only the female offspring were studied. Euthanasia occurred at PN180. Nic females showed hyperphagia, preference for a high-sucrose diet, increased anxiety-like behavior, lower tyrosine hydroxylase (TH), lower dopamine transporter and higher dopamine receptor (Drd2) in NAc; lower Drd1 in prefrontal cortex and lower TH in dorsal striatum (DS). These animals showed changes that can explain their hyperphagia, such as: lower leptin signaling pathway (Leprb, pJAK2, pSTAT3) and Chrna7 expression in hypothalamus. Neonatal nicotine exposure affects the brain reward system of the female progeny differently from males, mainly decreasing dopamine production in NAc and DS. Therefore, Nic females are more susceptible to develop food addiction and obesity.