Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS).

OBJECTIVES: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). METHODS: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. RESULTS: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. CONCLUSION: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.

Multimodal influences on learning walks in desert ants (Cataglyphis fortis).

Ants are excellent navigators using multimodal information for navigation. To accurately localise the nest at the end of a foraging journey, visual cues, wind direction and also olfactory cues need to be learnt. Learning walks are performed at the start of an ant's foraging career or when the appearance of the nest surrounding has changed. We investigated here whether the structure of such learning walks in the desert ant Cataglyphis fortis takes into account wind direction in conjunction with the learning of new visual information. Ants learnt to travel back and forth between their nest and a feeder, and we then introduced a black cylinder near their nest to induce learning walks in regular foragers. By doing this across days with different wind directions, we were able to probe how ants balance different sensory modalities. We found that (1) the ants' outwards headings are influenced by the wind direction with their routes deflected such that they will arrive downwind of their target, (2) a novel object along the route induces learning walks in experienced ants and (3) the structure of learning walks is shaped by the wind direction rather than the position of the visual cue.

In Vitro Antimicrobial Activity of Isopimarane-Type Diterpenoids.

The antimicrobial evaluation of twelve natural and hemisynthetic isopimarane diterpenes are reported. The compounds were evaluated against a panel of Gram-positive bacteria, including two methicillin-resistant Staphylococcus aureus (MRSA) strains and one vancomycin-resistant Enterococcus (VRE) strain. Only natural compounds 7,15-isopimaradien-19-ol (1) and 19-acetoxy-7,15-isopimaradien-3ß-ol (6) showed promising results. Isopimarane (1) was the most active, showing MIC values between 6.76 µM against S. aureus (ATCC 43866) and 216.62 µM against E. faecalis (FFHB 427483) and E. flavescens (ATCC 49996). Compound (6) showed moderated activity against all tested microorganisms (MIC between value 22.54 and 45.07 µM). These compounds were found to be active against the methicillin-sensitive strains of S. aureus (CIP 106760 and FFHB 29593), showing MIC values of 13.55 (1) and 22.54 (6) µM. Both compounds were also active against vancomycin-resistant E. faecalis (ATCC 51299) (MIC values of 54.14 and 45.07 µM, respectively). In addition, the cytotoxicity of nine compounds 7,15-isopimaradien-3ß,19-diol (2); mixture: 15-isopimarene-8ß-isobutyryloxy-19-ol and 15-isopimarene-8ß-butyryloxy-19-ol (3); 3ß-acetoxy-7,15-isopimaradiene-19-ol (5); 19-acetoxy-7,15-isopimaradiene-3ß-ol (6); 3ß,19-diacetoxy-7,15-isopimaradiene (8); 15-isopimarene-8ß,19-diol (9); 19-O-ß-d-glucopyranoside-7,15-isopimaradiene (10); lagascatriol-16-O-ß-d-glucopyranoside (11) and lagascatriol-16-O-α-d-mannopyranoside (12) was evaluated in the human breast cancer cell line MDA-MB-231. Isopimarane (2) was the only compound showing some cytotoxicity. The IC50 value of compound (2) was 15 µM, suggesting a mild antiproliferative activity against these breast cancer cells.

Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies.

BACKGROUND: Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. METHOD: Five different ILs were prepared-three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. RESULTS: Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. CONCLUSIONS: Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.

Unsaponifiable matter from oil of green coffee beans: cosmetic properties and safety evaluation.

CONTEXT: Unsaponifiable matter (UM), a fraction of green coffee oil (GCO) contains functional compounds responsible for desirable cosmetic properties such as UV-B absorption. OBJECTIVES: To evaluate oil content and sun protection factor (SPF) variability of the two most important species of coffee and, the toxic and cytotoxic effects, as well as cosmetic properties, including antioxidant and antimicrobial activities of UM obtained from green Coffea arabica seed oil. MATERIALS AND METHODS: The safety and potential cosmetic properties of UM extracted from green coffee oil (GCO) were evaluated by the brine shrimp viability and the MTT cytotoxicity assays. The SPF and antioxidant activity were evaluated using in vitro methods. RESULTS: Relevant cytotoxicity was found against keratinocytes for concentrations ≥25 µg/mL and in the brine shrimp assay (LC50 24 µg/mL). Antimicrobial and antioxidant activities (IC50 1448 µg/mL) were low in UM but SPF was 10 times higher than in GCO. CONCLUSION: UM is a novel potential UV-B absorbent but its use as a cosmetic ingredient should be better considered due to the considerable cytotoxicity shown in the experimental conditions described.

Genetic Variation of MT-ND Genes in Frontotemporal Lobar Degeneration: Biochemical Phenotype-Genotype Correlation.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is the second most common early-onset dementia. Over the last few decades, a growing number of evidence suggests mitochondrial involvement in neurodegeneration, namely modifications of mitochondrial DNA (mtDNA) contributing to energy impairment. OBJECTIVE: To sequence the 7 mitochondrially encoded complex I (MT-ND) genes in 70 FTLD patients and investigate mitochondrial respiratory chain (MRC) complex I activity. METHODS: A sample of 70 patients was studied (39 females and 31 males; age range: 38-82 years, mean ± SD: 63 ± 11 years) with a probable diagnosis of FTLD. Total DNA was extracted from peripheral blood, and sequencing analysis of 7 MT-NDn (1, 2, 3, 4L, 4, 5, 6) genes was performed. Variants identified were submitted to in silico study. Spectrophotometric evaluation of MRC activity in lymphocytes was performed, and results were compared with age-matched controls. RESULTS: A total of 358 (161 different) alterations were found in 92.9% of patients. According to in silico analysis of nonsynonymous variants, only 5 variations are possibly or probably damaging. Complex I activity is significantly decreased in patients. CONCLUSION: To our knowledge, this is the first report of the complete sequence of the MT-ND genes in FTLD patients and correlation with MRC activity. The high number of mtDNA variations identified and a significant decrease in complex I activity suggest a possible involvement of mtDNA alterations in FTLD. Although the majority of these alterations are not primarily pathogenic, an interaction with other mutations may occur, leading to the disease, worsening its expression or influencing age of onset.

Personal care products in soil-plant and hydroponic systems: Uptake, translocation, and accumulation.

Personal care products (PCPs) are organic compounds that are incorporated in several daily life products, such as shampoos, lotions, perfumes, cleaning products, air fresheners, etc. Due to their massive and continuous use and because they are not routinely monitored in the environment, these compounds are considered emerging contaminants. In fact, residues of PCPs are being discharged into the sewage system, reaching wastewater treatment plants (WWTPs), where most of these compounds are not completely degraded, being partially released into the environment via the final effluents and/or accumulating in the sewage sludges. Environmental sustainability is nowadays one of the main pillars of society and the application of circular economy models, promoting the waste valorisation, is increasingly encouraged. Therefore, irrigation with reclaimed wastewater or soil fertilization with sewage sludge/biosolids are interesting solutions. However, these practices raise concerns due to the potential risks associated to the presence of hazardous compounds, including PCPs. When applied to agricultural soils, PCPs present in these matrices can contaminate the soil or be taken up by crops. Crops can therefore become a route of exposure for humans and pose a risk to public health. However, the extent to which PCPs are taken up and bioaccumulated in crops is highly dependent on the physicochemical properties of the compounds, environmental variables, and the plant species. This issue has attracted the attention of scientists in recent years and the number of publications on this topic has rapidly increased, but a systematic review of these studies is lacking. Therefore, the present paper reviews the uptake, accumulation, and translocation of different classes of PCPs (biocides, parabens, synthetic musks, phthalates, UV-filters) following application of sewage sludge or reclaimed water under field and greenhouse conditions, but also in hydroponic systems. The factors influencing the uptake mechanism in plants were also discussed.

Antitumoral Activity of Cecropia Pachystachya Leaves Extract in Vitro and in Vivo Model of Rat Glioma: Brain and Blood Effects.

The aim of this study was to investigate the antiglioma effect of Cecropia pachystachya Trécul (CEC) leaves extract against C6 and U87 glioblastoma (GB) cells and in a rat preclinical GB model. The CEC extract reduced in vitro cell viability and biomass. In vivo, the extract decreased the tumor volume approximately 62%, without inducing systemic toxicity. The deficit in locomotion and memory and an anxiolytic-like behaviors induced in the GB model were minimized by CEC. The extract decreased the levels of reactive oxygen species, nitrites and thiobarbituric acid reactive substances and increased the activity of antioxidant enzymes in platelets, sera and brains of GB animals. The activity of NTPDases, 5'-nucleotidase and adenosine deaminase (ADA) was evaluated in lymphocytes, platelets and serum. In platelets, ATP and AMP hydrolysis was reduced and hydrolysis of ADP and the activity of ADA were increased in the control, while in CEC-treated animals no alteration in the hydrolysis of ADP was detected. In serum, the reduction in ATP hydrolysis was reversed by CEC. In lymphocytes, the increase in the hydrolysis of ATP, ADP and in the activity of ADA observed in GB model was altered by CEC administration. The observed increase in IL-6 and decrease in IL-10 levels in the serum of GB animals was reversed by CEC. These results demonstrate that CEC extract is a potential complementary treatment to GB, decreasing the tumor size, while modulating aspects of redox and purinergic systems.

Differential effects of methoxyamine on doxorubicin cytotoxicity and genotoxicity in MDA-MB-231 human breast cancer cells.

Pharmacological inhibition of DNA repair is a promising approach to increase the effectiveness of anticancer drugs. The chemotherapeutic drug doxorubicin (Dox) may act, in part, by causing oxidative DNA damage. The base excision repair (BER) pathway effects the repair of many DNA lesions induced by reactive oxygen species (ROS). Methoxyamine (MX) is an indirect inhibitor of apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional BER protein. We have evaluated the effects of MX on the cytotoxicity and genotoxicity of Dox in MDA-MB-231 metastatic breast cancer cells. MX has little effects on the viability and proliferation of Dox-treated cells. However, as assessed by the cytokinesis-block micronucleus assay (CBMN), MX caused a significant 1.4-fold increase (P<0.05) in the frequency of micronucleated binucleated cells induced by Dox, and also altered the distribution of the numbers of micronuclei. The fluorescence probe dihydroethidium (DHE) indicated little production of ROS by Dox. Overall, our results suggest differential outcomes for the inhibition of APE1 activity in breast cancer cells exposed to Dox, with a sensitizing effect observed for genotoxicity but not for cytotoxicity.

Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide.

Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000µM), GA markedly induced SCEs in a concentration-dependent manner up to concentrations of 750µM, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested.

Consumers' practices and safety perceptions regarding the use of materials for food preparation and storage: Analyses by age group.

Food Contact Materials (FCM) are those intended to be in contact with food, during its production, handling, and storage. FCM contain chemicals that could migrate to the foodstuff, posing potential health concerns, and usage practices influence the level of migration. This study assesses the preferences, safety perceptions, and usage practices of Portuguese consumers regarding FCM used for cooking and food storage (cookware). An observational, quantitative, and transversal study was performed through an online survey created for this purpose, which involved 1179 Portuguese adults. Results were analyzed according to age. Safety was the factor considered most important when choosing cookware materials, although the choice criteria varied with age. The majority of respondents recognize the risk of food contamination through cookware. Stainless steel and glass were considered the safest materials for cooking. The materials most used to reserve food are glass and plastic. Older individuals carry out more maintenance of cookware and have greater knowledge about how to wash and store it. Regarding the FCM symbology, there is a general lack of knowledge. Our study demonstrates the need to disseminate reliable information to the general public about cookware, contributing to greater literacy in health and to less exposure to food contact chemicals.

The Golgi Apparatus as an Anticancer Therapeutic Target.

Although the discovery of the Golgi apparatus (GA) was made over 125 years ago, only a very limited number of therapeutic approaches have been developed to target this complex organelle. The GA serves as a modification and transport center for proteins and lipids and also has more recently emerged as an important store for some ions. The dysregulation of GA functions is implicated in many cellular processes associated with cancer and some GA proteins are indeed described as cancer biomarkers. This dysregulation can affect protein modification, localization, and secretion, but also cellular metabolism, redox status, extracellular pH, and the extracellular matrix structure. Consequently, it can directly or indirectly affect cancer progression. For these reasons, the GA is an appealing anticancer pharmacological target. Despite this, no anticancer drug specifically targeting the GA has reached the clinic and few have entered the clinical trial stage. Advances in nanodelivery approaches may help change this scenario by specifically targeting tumor cells and/or the GA through passive, active, or physical strategies. This article aims to examine the currently available anticancer GA-targeted drugs and the nanodelivery strategies explored for their administration. The potential benefits and challenges of modulating and specifically targeting the GA function in the context of cancer therapy are discussed.

Predictive Factors of Tolerance in Office Hysteroscopy - a 3-Year Analysis from a Tertiary Center.

OBJECTIVE: Pain is the primary limitation to performing hysteroscopy. We aimed to evaluate the predictive factors of low tolerance to office hysteroscopic procedures. METHODS: Retrospective cohort study of the patients who underwent office hysteroscopy from January 2018 to December 2020 at a tertiary care center. Pain tolerance to office-based hysteroscopy was subjectively assessed by the operator as terrible, poor, moderate, good, or excellent. Categorical variables were compared with the use of the Chi-squared test; an independent-samples t-test was conducted to compare continuous variables. Logistic regression was performed to determine the main factors associated with low procedure tolerance. RESULTS: A total of 1,418 office hysteroscopies were performed. The mean age of the patients was 53 ± 13.8 years; 50.8% of women were menopausal, 17.8% were nulliparous, and 68.7% had a previous vaginal delivery. A total of 42.6% of women were submitted to an operative hysteroscopy. Tolerance was categorized as terrible or poor in 14.9% of hysteroscopies and moderate, good, or excellent in 85.1%. A terrible or poor tolerance was more frequently reported in menopausal women (18.1% vs. 11.7% in premenopausal women, p = 0.001) and women with no previous vaginal delivery (18.8% vs. 12.9% in women with at least one vaginal birth, p = 0.007). Low tolerance led more often to scheduling a second hysteroscopic procedure under anesthesia (56.4% vs. 17.5% in reasonable-to-excellent tolerance, p < 0.0005). CONCLUSION: Office hysteroscopy was a well-tolerated procedure in our experience, but menopause and lack of previous vaginal delivery were associated with low tolerance. These patients are more likely to benefit from pain relief measures during office hysteroscopy.

Genetic polymorphisms in detoxification and DNA repair genes and susceptibility to glycidamide-induced DNA damage.

Acrylamide (AA) is a probable human carcinogen formed in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), the AA metabolite formed by epoxidation, is considered the ultimate genotoxic agent. In this study, the in vitro genotoxic potential of AA and GA in human whole blood leukocytes was compared using the alkaline comet assay. Although AA did not induce significant DNA damage in the concentrations tested (up to 1000 µM), GA markedly increased the percentage of tail DNA at concentrations ≥250 µM. Further, this study addressed the role of genetic polymorphisms in key genes involved in metabolism and DNA repair pathways (BER, NER, HRR, and NHEJ) on GA-induced genotoxicity assessed by the alkaline comet assay. The results obtained suggested associations between DNA damage and polymorphisms of BER (MUTYH Gln335His and XRCC1 Gln399Arg) and NER (XPC Ala499Val) genes, either alone or in combination.

Redox-Active Molecules as Therapeutic Agents.

Oxidative stress and altered redox signaling have been described in a plethora of pathological conditions, such as inflammation, cardiovascular diseases, diabetes, cancer, and neurodegenerative disorders, among others [...].

GOLGI: Cancer cell fate control.

Growing evidence connects many of the Golgi known functions with cellular events related to cancer initiation and progression, including regulation of cell survival/death, proliferation, motility, metabolism and immune evasion. However, a broad and integrated understanding of the impact of the Golgi on cancer cell phenotype has not yet been achieved. Multiple cellular events involving the Golgi are associated with protein and lipid modification and trafficking. However, less explored aspects of this enigmatic organelle also contribute to cell fate decision-making by impacting signal transduction, redox and ion homeostasis. This article focuses on the molecular mechanisms and Golgi proteins underlying the impact of the Golgi on cancer cell phenotype. Special emphasis is given to emerging knowledge on redox and ion homeostasis. Current and potential cancer progression therapeutic strategies associated with this organelle will also be addressed.

Uptake and translocation of synthetic musk fragrances by pea plant grown in sewage sludge-amended soils.

Sewage sludges are rich in organic matter and several essential nutrients for plant growth, making them very appealing for application in agricultural soils. However, they may also contain a wide range of emerging pollutants, which has raised concerns about the potential risks of this practice to crops, the environment, and public health - accumulation in soils and/or plant uptake and translocation of contaminants. Therefore, there is a need to study plant-soil interactions and assess the uptake potential of these contaminants by food crops to better understand these risks. The main aim of this work was to assess the possible drawbacks of sludge application to cropland, by observing the impact on the growth and yield of a model crop (pea plant - Pisum sativum) grown over an 86-day greenhouse experiment and by assessing the uptake potential of synthetic musk fragrances. Different sewage sludge application rates (4-30-ton ha-1) and initial concentrations of contaminants were tested. The application of sludge yielded benefits to the cultivated plants, finding improved crop productivity with an application rate of 30-ton ha-1. At the end of the experiment, soil samples and plants separated into sections were analysed using a QuEChERS extraction methodology followed by gas chromatography-mass spectrometry (GC-MS) quantification. Galaxolide (HHCB) and tonalide (AHTN) underwent uptake by the plant roots, having been detected in concentrations up to 346 ng g-1 on a dry weight basis (dw), but only HHCB was detected in above ground tissues. At the end, a decrease in the levels of synthetic musks in the amended soils (>80% in several instances) was observed. Assuming the worst-case scenario, no risk to human health was observed from the ingestion of peas grown on sewage sludge-amended soils. However, a soil hazard quotient analysis yielded worryingly high quotient values for AHTN in nearly all tested conditions.

Plant uptake potential and soil persistence of volatile methylsiloxanes in sewage sludge amended soils.

Volatile methylsiloxanes (VMSs) are organosilicon compounds, ubiquitous in modern life. Due to their high use in consumer products, large amounts of these compounds are released into sewer systems, reaching wastewater treatment plants (WWTPs). Its frequent detection in sewage sludge can be of concern when considering its land application, not only due to potential negative impacts on the environment, but also on human health. In this work, the effects of sewage sludge application on plant development and crop productivity were studied, as well as VMSs persistence in the soil and their plant uptake. This study focused on 7 VMSs (D3, D4, D5, D6, L3, L4 and L5) and consisted of a 12-week greenhouse pot experiment, where sewage sludge-amended soils were used to cultivate Pisum sativum (peas). Sewage sludge application to soils had no negative effects on plant development and was tied to crop productivity improvements. Most of the VMSs were still present in soils at the end of the experiment and plant uptake and translocation of the 4 cyclic VMSs (D3, D4, D5, D6) occurred. VMSs were detected in plant tissues up to 161 ± 27 ng g-1 dw (samples of stems, leaves and tendrils), but did not exceed 50 ± 19 ng g-1 dw in peas, which did not translate into a human exposure risk due to ingestion, according to an intake risk assessment. However, soil risk assessments showed that for L5 the hazardous ratios were higher than the threshold value of 1. This means a potential environmental risk despite the low levels of this compound in soils (up to 7.3 ± 0.7 ng g-1 dw). Considering these results, sewage sludge monitoring plans should be defined for VMSs, namely when its final destination is land application, thus allowing a safer management of this residue, taking advantage of its valorization potential.

The Perception of Primary School Teachers Regarding the Pharmacotherapy of Attention Deficit Hyperactivity Disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is raising concerns across health systems, affecting about 5% of the school-age population. Therapy usually involves psychostimulants, which are prone to adverse drug reactions (ADRs). Teachers have many contact hours with children and can easily detect behavioral changes upon the beginning of medication. However, few studies have focused on the role of teachers in the management of ADHD children and detection of ADRs. The present work aimed to characterize the perception of primary school teachers regarding the impact of ADHD therapeutics. A questionnaire was constructed focused on teachers' training regarding ADHD and its therapy; experience with students with ADHD; changes upon beginning of medication; and observation of ADRs. A total of 107 completed questionnaires were obtained. The results indicate that more than 40% of the inquired teachers have received training in ADHD, but in most cases, the theme of therapeutics was absent from that training. The vast majority of teachers (91.6%) have had students with ADHD and observed mood alterations associated with medications. More than 60% of the teachers answered that they are aware of the ADRs and of these, 24% have already detected them in their students. The teachers reported the observed ADRs to parents in 93% of the cases and to doctors in 28% of the cases. In conclusion, the results show the need to reinforce teachers' training in ADHD and its therapeutics.

Hyperandrogenism, oligomenorrhea, and erythrocytosis caused by an ovarian Leydig cell tumor: A case report.

Leydig cell tumors are rare ovarian neoplasms. Affected individuals typically present with amenorrhea/oligomenorrhea and rapidly progressive features of virilization. Erythrocytosis can also occur as a result of high testosterone levels.