Insight into the efficiency of microalgae' lipidic extracts as photosensitizers for Antimicrobial Photodynamic Therapy against Staphylococcus aureus.

Antibacterial resistance causes around 1.27 million deaths annually around the globe and has been recognized as a top 3 priority health threat. Antimicrobial photodynamic therapy (aPDT) is considered a promising alternative to conventional antibiotic treatments. Algal lipid extracts have shown antibacterial effects when used as photosensitizers (PSs) in aPDT. In this work we assessed the photodynamic efficiency of lipidic extracts of microalgae belonging to different phyla (Bacillariophyta, Chlorophyta, Cyanobacteria, Haptophyta, Ochrophyta and Rhodophyta). All the extracts (at 1 mg mL-1) demonstrated a reduction of Staphylococcus aureus >3 log10 (CFU mL-1), exhibiting bactericidal activity. Bacillariophyta and Haptophyta extracts were the top-performing phyla against S. aureus, achieving a reduction >6 log10 (CFU mL-1) with light doses of 60 J cm-2 (Bacillariophyta) and 90 J cm-2 (Haptophyta). The photodynamic properties of the Bacillariophyta Phaeodactylum tricornutum and the Haptophyta Tisochrysis lutea, the best effective microalgae lipid extracts, were also assessed at lower concentrations (75 µg mL-1, 7.5 µg mL-1, and 3.75 µg mL-1), reaching, in general, inactivation rates higher than those obtained with the widely used PSs, such as Methylene Blue and Chlorine e6, at lower concentration and light dose. The presence of chlorophyll c, which can absorb a greater amount of energy than chlorophylls a and b; rich content of polyunsaturated fatty acids (PUFAs) and fucoxanthin, which can also produce ROS, e.g. singlet oxygen (1O2), when photo-energized; a lack of photoprotective carotenoids such as ß-carotene, and low content of tocopherol, were associated with the algal extracts with higher antimicrobial activity against S. aureus. The bactericidal activity exhibited by the extracts seems to result from the photooxidation of microalgae PUFAs by the 1O2 and/or other ROS produced by irradiated chlorophylls/carotenoids, which eventually led to bacterial lipid peroxidation and cell death, but further studies are needed to confirm this hypothesis. These results revealed the potential of an unexplored source of natural photosensitizers (microalgae lipid extracts) that can be used as PSs in aPDT as an alternative to conventional antibiotic treatments, and even to conventional PSs, to combat antibacterial resistance.

Determination of Selected Metals and Metalloids in Different Types of Rice by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES).

Pantanal is a unique biome located in Brazil, with diverse fauna and flora, being home to native species such as the rice types Oryza latifolia and Oryza rufipogon. Rice is a staple food for two-thirds of the population, with increasing consumption, especially in Asia, regions of Sub-Saharan Africa, countries in the Caribbean, and Latin America. The per capita rice consumption had an average consumption of 160 g/day. However, rice consumption may lead to the intake of other harmful substances to health, such as toxic metals/metalloids. The determination of potential hazards in native species is crucial in maintaining the local population in good health. In this study, we determined the concentration of essential elements and potentially toxic elements in seven different types of Brazilian rice grains, including the two Pantanal native species O. latifolia and O. rufipogon, using ICP-OES to identify their nutritional richness or potential toxicity. The contaminant with the highest HQ levels was chromium, with an HQ above one only in the native species. All species (commercial and native) showed carcinogenic risk considering inorganic arsenic. Rice exhibits duality in its classification, providing nutritional content and leading people to potential risks of overexposure to toxic elements. While rice can be part of a healthy and nutritious diet, more studies should be conducted on avoiding or remedying contamination with toxic elements.

Chlorella vulgaris and Tetradesmus obliquus Protect Spinach (Spinacia oleracea L.) against Fusarium oxysporum.

Chlorella vulgaris and Tetradesmus obliquus were tested as biocontrol agents against the phytopathogenic fungus Fusarium oxysporum. This evaluation was conducted through in vitro and in vivo trials with spinach (Spinacia oleracea L.). The in vitro trials showed that C. vulgaris and T. obliquus were able to inhibit the phytopathogen, showing a similar inhibitory effect to that of the positive controls (Rovral, BASF® and Biocontrol T34, Biocontrol Technologies® S.L.). C. vulgaris aqueous suspensions at 3.0 g L-1 led to a hyphal growth of 0.55 cm, each corresponding to a reduction of 63% of fungal growth. With T. obliquus, the hyphal growth was 0.53 cm when applied at a concentration of 0.75 g L-1, having an inhibition of fungus growth of 64%. Thereafter, these results were validated in an in vivo trial on spinach using the same controls. The results revealed a lower severity and disease incidence and a reduction in the disease's AUDPC (area under the disease progress curve) when spinach was treated with the microalgae suspensions. Overall, these findings highlight the potential of C. vulgaris and T. obliquus suspensions as promising biocontrol agents against F. oxysporum in spinach when applied through irrigation.

A new trypsin inhibitor from Centrosema plumieri effective against digestive proteases from Tribolium castaneum, an eco-friendly alternative.

Tribolium castaneum, also known as the red flour beetle, is a polyphagous pest that seriously damages agricultural products, including stored and processed grains. Researchers have aimed to discover alternative pest control mechanisms that are less harmful to the ecosystem than those currently used. We conduct the purification and characterization of a protease inhibitor from C. plumieri seeds and an in vitro evaluation of its insecticidal potential against the insect pest T. castaneum. The trypsin inhibitor was isolated from C. plumieri seeds in a single-step DEAE-Sepharose column chromatography and had a molecular mass of 50 kDA. When analyzed for interaction with different proteolytic enzymes, the inhibitor exhibited specificity against trypsin and no activity against other serine proteases such as chymotrypsin and elastase-2. The isolated inhibitor was able to inhibit digestive enzymes of T. castaneum from extracts of the intestine of this insect. Therefore, we conclude that the new protease inhibitor, specific in tryptic inhibition, of protein nature from the seeds of C. plumieri was effective in inhibiting the digestive enzymes of T. castaneum and is a promising candidate in the ecological control of pests.

Physical function as a marker to assess the effects of occupational long-term pesticide exposure.

In this cross-sectional study, we determined the relative impact of long-term occupational exposure to pesticides on physical performance and perception of tiredness. Experimental data was collected in locus from agricultural communities and included surveys to assess the duration of exposure to pesticides, social status, habitual physical activity levels, presence of common mental disorders (CMD), and self-reported tiredness. Plasmatic cholinesterase (PChE), body composition and traditional functional performance tests (Handgrip strength-HGS; Time up and go-TUG; and Sit-to-stand-STS) were obtained. From the 127 individuals tested, cluster analysis yielded 80 individuals divided in Direct Exposed (n = 37) and Indirect Exposed (n = 43); Tired (n = 16), and Not Tired (n = 64). PChE values were within the reference values (5209.64-13943.53 U/L). Pesticide exposure had no influence on PChE levels, CMD or fatigue (p > 0.05), while Self-reported tiredness had (p < 0.05). Principal Component Analyses showed that HGS; STS and TUG (i.e., physical performance variables) are negatively influenced by two independent factors: pesticide exposure and self-reported tiredness. We conclude that chronic pesticide exposure and tiredness can negatively impact physical performance, independently, without clinically significant changes in PChE levels that is a biomarker used to track pesticide intoxication. Functional physical tests can be a useful tool to identify chronic pesticide exposure, and help with the limitations of commonly used parameters (i.e. PChE and CMD). Self-reported tiredness is a confounding variable.

Early-life factors shaping the gut microbiota of Common buzzard nestlings.

BACKGROUND: Exploring the dynamics of gut microbiome colonisation during early-life stages is important for understanding the potential impact of microbes on host development and fitness. Evidence from model organisms suggests a crucial early-life phase when shifts in gut microbiota can lead to immune dysregulation and reduced host condition. However, our understanding of gut microbiota colonisation in long-lived vertebrates, especially during early development, remains limited. We therefore used a wild population of common buzzard nestlings (Buteo buteo) to investigate connections between the early-life gut microbiota colonisation, environmental and host factors. RESULTS: We targeted both bacterial and eukaryotic microbiota using the 16S and 28S rRNA genes. We sampled the individuals during early developmental stages in a longitudinal design. Our data revealed that age significantly affected microbial diversity and composition. Nest environment was a notable predictor of microbiota composition, with particularly eukaryotic communities differing between habitats occupied by the hosts. Nestling condition and infection with the blood parasite Leucocytozoon predicted microbial community composition. CONCLUSION: Our findings emphasise the importance of studying microbiome dynamics to capture changes occurring during ontogeny. They highlight the role of microbial communities in reflecting host health and the importance of the nest environment for the developing nestling microbiome. Overall, this study contributes to understanding the complex interplay between microbial communities, host factors, and environmental variables, and sheds light on the ecological processes governing gut microbial colonisation during early-life stages.

Cardiovascular benefits of resistance exercise: It's time to prescribe.

Despite the well-known health benefits of regular physical activity, sedentary behavior and physical inactivity remain a real global pandemic. Exercise is associated with increased life expectancy, improved quality of life and prevention of multiple diseases. Although less implemented in practice compared to aerobic exercise, recent evidence shows that resistance exercise (RE) is also responsible for various benefits, including improvements in body composition, control of several cardiovascular (CV) risk factors, and reduction of CV outcomes. RE increases strength and muscle mass, is effective in controlling type 2 diabetes, and improves the management of obesity, lipids, and blood pressure profiles. In this setting, clinical guidelines recommend the inclusion of RE for primary and secondary CV risk prevention, particularly in combination with aerobic exercise, in which the benefits are most pronounced. Prescription of RE should follow a methodology that includes key variables such as frequency, intensity, type, time, and progression. Despite challenges, professionals in the CV field should be familiar with RE prescription in order to maximize its referral in clinical practice. This review aims to analyze the CV effects of RE and current recommendations regarding the prescription of this type of exercise.

Concurrent validity between field tests and cardiopulmonary exercise testing in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Maximal treadmill cardiopulmonary exercise testing is the gold standard for assessing functional capacity in patients with idiopathic pulmonary fibrosis (IPF). PURPOSE: Primarily to investigate the concurrent validity between three field tests and cardiopulmonary exercise testing in these patients. METHODS: Patients performed the cardiopulmonary exercise testing, a six-minute walk test, an incremental shuttle walk test, and, the Glittre-ADL test. For cardiopulmonary exercise testing, the ten seconds with the higher average of the peak oxygen uptake obtained within the last 30 seconds were considered; for six-minute walk test and incremental shuttle walk test, the longer distance; and for the Glittre-ADL test, the shorter time spent. Concurrent validity was assessed using different regression models based on the best adjustment of the data. RESULTS: Twenty-two patients with IPF were assessed, aged: 68 ± 8.1 years, 13 male. Patients presented a peak oxygen uptake of 16.5 ± 3.6 mL.kg-1.min1, achieving a distance of 512.6 ± 102.8 meters in the six-minute walk test and 415.7 ± 125.1 meters in incremental shuttle walk test. The walking distance in the six-minute walk test and the incremental shuttle walk test explained, respectively, 64% and 56% peak oxygen uptake variance observed in the cardiopulmonary exercise testing (R2 = 0.64,p < .001; R2 = 0.56,p < .001). The time spent in the Glittre-ADL test was 233.4 ± 88.7 seconds and explained 47% of the peak oxygen uptake variance observed in cardiopulmonary exercise testing (R2 = 0.47,p = .001). CONCLUSION: The six-minute walk test, incremental shuttle walk test, and Glittre-ADL test were considered valid tests to explain the peak oxygen uptake variance obtained by the cardiopulmonary exercise testing in patients with IPF.

Comparison of Different Pretreatment Processes Envisaging the Potential Use of Food Waste as Microalgae Substrate.

A significant fraction of the food produced worldwide is currently lost or wasted throughout the supply chain, squandering natural and economic resources. Food waste valorization will be an important necessity in the coming years. This work investigates the ability of food waste to serve as a viable nutritional substrate for the heterotrophic growth of Chlorella vulgaris. The impact of different pretreatments on the elemental composition and microbial contamination of seven retail food waste mixtures was evaluated. Among the pretreatment methods applied to the food waste formulations, autoclaving was able to eliminate all microbial contamination and increase the availability of reducing sugars by 30%. Ohmic heating was also able to eliminate most of the contaminations in the food wastes in shorter time periods than autoclave. However, it has reduced the availability of reducing sugars, making it less preferable for microalgae heterotrophic cultivation. The direct utilization of food waste containing essential nutrients from fruits, vegetables, dairy and bakery products, and meat on the heterotrophic growth of microalgae allowed a biomass concentration of 2.2 × 108 cells·mL-1, being the culture able to consume more than 42% of the reducing sugars present in the substrate, thus demonstrating the economic and environmental potential of these wastes.

Reliability and Validity of Maximal Respiratory Pressures.

BACKGROUND: Maximal respiratory pressure is used to assess the inspiratory and expiratory muscles strength by using maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax). This study aimed to summarize and evaluate the reliability and validity of maximal respiratory pressure measurements. METHODS: This systematic review followed the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations and was reported by using the PRISMA checklist. Studies published before March 2023 were searched in PubMed and EMBASE databases. RESULTS: A total of 642 studies were identified by using the online search strategy and manual search (602 and 40, respectively). Twenty-three studies were included. The level of evidence for test-retest reliability was moderate for PImax and PEmax (intraclass correlation coefficient > 0.70 for both), inter-rater reliability was low for PImax and very low for PEmax (intraclass correlation coefficient > 0.70 for both), and the measurement error was very low for PImax and PEmax. In addition, concurrent validity presented a high level of evidence for PImax and PEmax (r > 0.80). CONCLUSIONS: Only concurrent validity of maximal respiratory pressure measured with the manometers evaluated in this review presented a high level of evidence. The quality of clinical studies by using maximal respiratory pressure would be improved if more high-quality studies on measurement properties, by following well established guidelines and the COSMIN initiative, were available.

Influence of visual feedback and cognitive challenge on the age-related changes in force steadiness.

Force steadiness can be influenced by visual feedback as well as presence of a cognitive tasks and potentially differs with age and sex. This study determined the impact of altered visual feedback on force steadiness in the presence of a difficult cognitive challenge in young and older men and women. Forty-nine young (19-30 yr; 25 women, 24 men) and 25 older (60-85 yr; 15 women; 10 men) performed low force (5% of maximum) static contractions with the elbow flexor muscles in the presence and absence of a cognitive challenge (counting backwards by 13) either with low or high visual feedback gain. The cognitive challenge reduced force steadiness (increased force fluctuation amplitude) particularly in women (cognitive challenge × sex: P < 0.05) and older individuals (cognitive challenge × age: P < 0.05). Force steadiness improved with high-gain visual feedback compared with low-gain visual feedback (P < 0.01) for all groups (all interactions: P > 0.05). Manipulation of visual feedback had no influence on the reduced force steadiness in presence of the cognitive challenge for all groups (all P > 0.05). These findings indicate that older individuals and women have greater risk of impaired motor performance of the upper extremity if steadiness is required during a low-force static contraction. Manipulation of visual feedback had minimal effects on the reduced force steadiness in presence of a difficult cognitive challenge.

Delayed-Onset Muscle Soreness Alters Mechanical Sensitivity, but Not Thermal Sensitivity or Pain Modulatory Function.

Introduction: Many clinical musculoskeletal pain conditions are characterized by chronic inflammation that sensitizes nociceptors. An unresolved issue is whether inflammation affects all nociceptors in a similar manner. Exercise-induced muscle damage (EIMD) has been proposed as a model for simulating clinical inflammatory pain in healthy samples. We sought to test the effect of EIMD on various painful stimuli (pressure and thermal), central pain processing (via the nociceptive flexion reflex) and endogenous pain modulation via conditioned pain modulation and exercise-induced hypoalgesia. Methods: Eighteen participants (9F, age: 24.6 ± 3.3) were recruited for repeated measures testing and each completed pain sensitivity testing prior to and 48 hours after an eccentric exercise protocol. The participants performed a minimum of 6 rounds of 10 eccentric knee extension exercises to induce muscle damage and localized inflammation in the right quadriceps. Force decrements, knee range-of-motion, and delayed onset muscle soreness (DOMS) were used to quantify EIMD. Results: There was a significant main effect of time for pressure pain (%diff; -58.9 ± 23.1; p = 0.02, ηp2 = 0.28) but no significant main effect was observed for limb (%diff; -15.5 ± 23.9; p = 0.53, ηp2 = 0.02). In contrast, there was a significant interaction between time and limb (p < 0.001, ηp2 = 0.47) whereby participants had lower pressure pain sensitivity in the right leg only after the damage protocol (%diff; -105.9 ± 29.2; p = 0.002). Discussion: Individuals with chronic inflammatory pain usually have an increased sensitivity to pressure, thermal, and electrical stimuli, however, our sample, following muscle damage to induce acute inflammation only had sensitivity to mechanical pain. Exercise induced inflammation may reflect a peripheral sensitivity localized to the damaged muscle rather than a global sensitivity like those with chronic pain display.

Optimization of enzymatic saccharification of industrial wastes using a thermostable and halotolerant endoglucanase through Box-Behnken experimental design.

This study describes the production, characterization and application of an endoglucanase from Penicillium roqueforti using lignocellulosic agro-industrial wastes as the substrate during solid-state fermentation. The endoglucanase was generated after culturing with different agro-industrial wastes for 96 h without any pretreatment. The highest activity was obtained at 50 °C and pH 4.0. Additionally, the enzyme showed stability in the temperature and pH ranges of 40-80 °C and 4.0-5.0, respectively. The addition of Ca2+, Zn2+, Mg2+, and Cu2+ increased enzymatic activity. Halotolerance as a characteristic of the enzyme was confirmed when its activity increased by 35% on addition of 2 M NaCl. The endoglucanase saccharified sugarcane bagasse, coconut shell, wheat bran, cocoa fruit shell, and cocoa seed husk. The Box-Behnken design was employed to optimize fermentable sugar production by evaluating the following parameters: time, substrate, and enzyme concentration. Under ideal conditions, 253.19 mg/g of fermentable sugars were obtained following the saccharification of wheat bran, which is 41.5 times higher than that obtained without optimizing. This study presents a thermostable, halotolerant endoglucanase that is resistant to metal ions and organic solvents with the potential to be applied in producing fermentable sugars for manufacturing biofuels from agro-industrial wastes.

Are images worth a thousand words? A preliminary study testing a video for owner education in canine atopic dermatitis.

BACKGROUND: Successful management of canine atopic dermatitis (cAD) is challenging and effective pet owner education is crucial to successful outcomes. However, there are limited proven educational strategies in this area. Our goal was to create an effective and engaging educational tool for owners of dogs with cAD. HYPOTHESIS: Video-based education efficacy would be comparable to traditional verbal delivery. Secondary objectives included assessing client perception of the intervention, and determining if there were clinical benefits for the dogs and improved client adherence to treatment. SUBJECTS: Twenty-nine dogs with cAD and their owners were recruited from a teaching hospital of a European veterinary medicine faculty. MATERIALS AND METHODS: In this 8 week, prospective, randomised controlled study, clients in the control group (CG, n = 13) received verbal education and those in the intervention group (IG, n = 16) watched a video. Client knowledge was assessed at Day (D)0 and D56. Treatment adherence and perceived utility and appeal ratings were measured at D56. Clinical progress was assessed at D0 and D56 using CADESI-04 and PVAS10. RESULTS: The differences found in the means of cAD knowledge score, clinical outcomes, utility and appeal ratings and owners' adherence score between groups were not statistically significant. A significant association between the outcome and the intervention group concerning education success [CG, six of 13 (46.15%); IG, 15 of 16 (93.75%)] was found (p = 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Video-based instructions positively impacted owners' education and demonstrated their potential as a valuable tool. The authors believe that video-based education could be a time-efficient alternative for initial cAD education in veterinary clinics.

Perianal Tuberculosis in an Immunocompetent Patient: Exploring the Uncommon Manifestation

Abstract As it is an infrequent etiology, the diagnosis of perianal tuberculosis is challenging, especially in the absence of a pulmonary focus. TB should be considered in the differential diagnosis of perianal ulcers, fistulas, abscesses, mainly in non-healing and recurrent anal lesions. Treatment with anti-TB agents can provide complete recovery. Furthermore, these lesions are often diagnosed later after complete histopathological and mycobacterial results, where the benefit of avoiding morbid multiple surgeries by effective anti-TB treatment is lost. We reported a rare case of an immuno-competent patient with perianal TB, which was the first manifestation of the disease. A fit-and-well man in his 20s presented a large perianal abscess. Unexpectedly, his chest X-ray showed a rounded hyper-transparency in the left lung. The abscess was drained. Posterior investigation with culture analysis from pus swabs and sputum revealed the presence of Mycobacterium tuberculosis complex infection. After completing the 6 months of oral administration of anti-TB drugs, the patient was asymptomatic. By highlighting this unusual manifestation, we aim to improve clinicians' awareness of perianal TB, facilitating early recognition and appropriate management.

Purification and characterization of a new trypsin-like protease from Crotalaria stipularia.

Proteases are the main enzymes traded worldwide-comprising 60% of the total enzyme market-and are fundamental to the degradation and processing of proteins and peptides. Due to their high commercial demand and biological importance, there is a search for alternative sources of these enzymes. Crotalaria stipularia is highlighted for its agroecological applications, including organic fertilizers, nematode combat, and revegetation of areas contaminated with toxic substances. Considering the pronounced biotechnological functionality of the studied species and the necessity to discover alternative sources of proteases, we investigated the extraction, purification, and characterization of a protease from seeds of the C. stipularia plant. Protease isolation was achieved by three-phase partitioning and single-step molecular exclusion chromatography in Sephacryl S-100, with a final recovery of 47% of tryptic activity. The molecular mass of the isolated enzyme was 40 kDa, demonstrating optimal activities at pH 8.0 and 50 °C. Enzymatic characterization demonstrated that the protease can hydrolyze the specific trypsin substrate, BApNA. This trypsin-like protease had a Km, Vmax, Kcat, and catalytic efficiency constant of 0.01775 mg/mL, 0.1082 mM/min, 3.86 s-1, and 217.46, respectively.

Impact of a wearable-based physical activity and sleep intervention in multimorbidity patients: protocol for a randomized controlled trial.

BACKGROUND: The benefits of physical activity (PA) and adequate sleep are well documented, and their importance strengthens with the increasing prevalence of chronic diseases and multimorbidity (MM). Interventions to promote physical activity and sleep that use commercial activity trackers may be useful non-pharmacological approaches to managing individual health; however, limited evidence exists on their use to improve physical activity in older adult patients with MM. METHODS: This study aims to measure the effects of behavioral change techniques (BCTs) delivered by a wearable device on physical activity and quality of sleep (QS) in older adult patients with MM. We designed an open-label randomized controlled trial with participants recruited through primary care and a specialist outpatient clinic. Participants must be more than 65 years old, have MM, and have access to smartphones. All eligible participants will receive PA promotion content and will be randomly assigned to wear a smartwatch. The primary outcome will be the participants' PA measurement at baseline and at six months using the International Physical Activity Questionnaire - Short Form (IPAQ-SF). Secondary outcomes will include changes in the participants' frailty status, biometric measurements, quality of life, and biopsychosocial assessments. A sample size of 40 participants per arm was calculated to detect group differences, with 50 participants planned to recruit and randomize into each arm. DISCUSSION: This study aims to contribute to a better understanding of PA patterns and the impact of wearable-based PA interventions in patients with MM. In addition, we aim to contribute to more knowledge about the relationship between PA patterns, Patient Reported Outcomes Measures (PROMs), and healthcare resource utilization in patients with MM. To achieve this, the study will leverage a locally developed PROMs registry and assess data from participants' medical records, in order to understand the added impact of wearable data and medical information data on predicting PROMs and unplanned hospital admissions. TRIAL REGISTRATION: NCT05777291.

Subcentimetric papillary thyroid carcinoma with extensive lymph node and brain metastasis: case report and review of literature.

Summary: We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case. Learning points: Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival. PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome. Brain metastasis although rare indicate aggressive phenotypic features. Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.