Routine regularity during a global pandemic: Impact on mental health outcomes and influence of chronotype.

Among the public health recommendations for supporting mental health during the COVID-19 pandemic, many strategies had an impact on biological rhythms, like sleep hygiene, physical exercise and healthy eating habits. Considering the known relationship between circadian organization and mental health, our aim was to test the association between behavioral regularity and mental health, and its interaction with chronotype, in a large sample surveyed in Brazil. We collected longitudinal data using online questionnaires that assessed sociodemographic characteristics, behavioral routines, mental health (PHQ-9, GAD-7, WHO-5 scales), and chronotype estimation based on midpoint of sleep on free days - MSF (µMCTQ), in a sample of 1390 participants (81% females). We computed a Routine Regularity Score (RRS) that reflects regularity across four behaviors: sleep, eating, working, exercising. There was a strong negative association between RRS and the severity of anxiety and depressive symptoms (GAD-7 and PHQ-9 scores), which was weaker among participants with late MSF, and a strong positive association with well-being (WHO-5 scores). RRS was a mediator of the MSF-mental health association and a predictor of mental health states. This study provides empirical evidence that maintaining behavioral routines during times of hardship may serve as tools to alleviate the negative impact on mental health.

Pressurized liquid extraction of bioactive compounds from grape peel and application in pH-sensing carboxymethyl cellulose films: A promising material to monitor the freshness of pork and milk.

This study produced pH-sensing carboxymethyl cellulose (CMC) films functionalized with bioactive compounds obtained by pressurized liquid extraction (PLE) of grape peel to monitor the freshness of pork and milk. A semi-continuous PLE was conducted using hydroethanolic solution (70:30, v/v) at a flow rate of 5 mL/min, 15 MPa, and 60 °C. The films were produced by the casting technique using CMC (2.5 %, w/v), glycerol (1 %, v/v), and functionalized with 10, 30, and 50 % (v/v) grape peel extract. From the results obtained, LC-MS/MS revealed that PLE extracted twenty-seven phenolic compounds. The main phenolic compounds were kaempferol-3-glucoside (367.23 ± 25.88 µg/mL), prunin (270.23 ± 3.62 µg/mL), p-coumaric acid (236.43 ± 26.02 µg/mL), and procyanidin B1 (117.17 ± 7.29 µg/mL). The CMC films presented suitable color and mechanical properties for food packaging applications. The addition of grape peel extract promoted the pH-sensing property, showing the sensitivity of anthocyanins to pH changes. The films functionalized with grape peel extract presented good release control of bioactive compounds, making them suitable for food packaging applications. When applied to monitor the freshness of pork and milk, the films exhibited remarkable color changes associated with the pH of the food during storage. In conclusion, PLE is a sustainable approach to obtaining bioactive compounds from the grape peel, which can be applied in the formulation of pH-sensing films as a promising sustainable material to monitor food freshness during storage.

A step forward on the in vitro and in vivo assessment of a novel nanomedicine against melanoma.

Melanoma is the most aggressive form of skin cancer, with increasing incidence and mortality rates. To overcome current treatment limitations, a hybrid molecule (HM) combining a triazene and a sulfur L-tyrosine analogue, was recently synthesized, incorporated in long blood circulating liposomes (LIP HM) and validated in an immunocompetent melanoma model. The present work constitutes a step forward in the therapeutic assessment of HM formulations. Here, human melanoma cells, A375 and MNT-1, were used and dacarbazine (DTIC), a triazene drug clinically available as first-line treatment for melanoma, constituted the positive control. In cell cycle analysis, A375 cells, after 24-h incubation with HM (60 µM) and DTIC (70 µM), resulted in a 1.2 fold increase (related to control) in the percentage of cells in G0/G1 phase. The therapeutic activity was evaluated in a human murine melanoma model (subcutaneously injected with A375 cells) to most closely resemble the human pathology. Animals treated with LIP HM exhibited the highest antimelanoma effect resulting in a 6-, 5- and 4-fold reduction on tumor volume compared to negative control, Free HM and DTIC groups, respectively. No toxic side effects were detected. Overall, these results constitute another step forward in the validation of the antimelanoma activity of LIP HM, using a murine model that more accurately simulates the pathology that occurs in human patients.

Preclinical validation of a new hybrid molecule loaded in liposomes for melanoma management.

The aggressiveness of melanoma and lack of effective therapies incite the discovery of novel strategies. Recently, a new dual acting hybrid molecule (HM), combining a triazene and a ʟ-tyrosine analogue, was synthesized. HM was designed to specifically be activated by tyrosinase, the enzyme involved in melanin biosynthesis and overexpressed in melanoma. HM displayed remarkable superior antiproliferative activity towards various cancer cell lines compared with temozolomide (TMZ), a triazene drug in clinical use, that acts through DNA alkylation. In B16-F10 cells, HM induced a cell cycle arrest at phase G0/G1 with a 2.8-fold decrease in cell proliferation index. Also, compared to control cells, HM led to a concentration-dependent reduction in tyrosinase activity and increase in caspase 3/7 activity. To maximize the therapeutic performance of HM in vivo, its incorporation in long blood circulating liposomes, containing poly(ethylene glycol) (PEG) at their surface, was performed for passively targeting tumour sites. HM liposomes (LIP HM) exhibited high stability in biological fluids. Preclinical studies demonstrated its safety for systemic administration and in a subcutaneous murine melanoma model, significantly reduced tumour progression. In a metastatic murine melanoma model, a superior antitumour effect was also observed for mice receiving LIP HM, with markedly reduction of lung metastases compared to positive control group (TMZ). Biodistribution studies using 111In-labelled LIP HM demonstrated its ability for passively targeting tumour sites, thus correlating with the high therapeutic effect observed in the two experimental murine melanoma models. Overall, our proposed nanotherapeutic strategy was validated as an effective and safe alternative against melanoma.

Cannabis use in Attention - Deficit/Hyperactivity Disorder (ADHD): A scoping review.

INTRODUCTION: Treatments for Adult ADHD include stimulants, two non-stimulant medications, as well as cognitive-behavioral therapy (CBT). These pharmacological agents are often associated with side effects, contributing to poor treatment adherence. Patients with ADHD have regularly stated that cannabis has helped improve their ADHD symptoms; however, scientific literature describing the effects of cannabis on symptoms of ADHD is scarce. METHODS: We systematically searched MEDLINE, EMBASE, EMCARE, PsycINFO, Web of Science, Cochrane Library, and Clinicaltrials.gov. The searches included all publications in English up to June 27, 2022. We included both experimental and observational studies that assessed the effect of cannabis on ADHD symptomatology and neuropsychiatric outcomes. To synthesize our current understanding of the potential effects of cannabis use on ADHD symptoms and pathophysiology, and the effects of ADHD on cannabis use, data was extracted from each study regarding the characteristics of its population, methods used to assess both cannabis consumption and ADHD symptoms, and key findings. RESULTS: Our scoping review included a total of 39 studies. Only one study employed a randomized and placebo-controlled design to directly measure the effect of cannabis on ADHD, and no significant effect was observed for the study's primary outcome, the QbTest (Est = -0.17, 95% CI -0.40 to 0.07, p = 0.16). Most of the literature consists of cross-sectional studies that evaluate the association between ADHD severity and cannabis use. 15 studies addressed the neuropsychiatric effects of cannabis on ADHD by employing either a battery of neuropsychiatric tests or neuroimaging. The concentration and amount of THC and CBD used were not well measured in most of the studies. Although some studies indicated that cannabis improved ADHD symptoms, most studies indicated it worsened or had no effect on ADHD symptoms. CONCLUSIONS: Given the current evidence, cannabis is not recommended for people with ADHD. Limitations of the literature include the absence of objective measurements for cannabis exposure and ADHD symptoms, heterogenous definitions, oversampling, and small sample sizes.

Self-perceived rhythmicity in affective and cognitive functions is related to psychiatric symptoms in adolescents.

The objective of this study was to evaluate the relationship between self-perceived rhythms measured using the Mood Rhythm Instrument for adolescents (MRhI-Y) and depressive and psychiatric symptoms measured with the Children's Depressive Instrument (CDI) and the Strengths and Difficulties Questionnaire (SDQ). In this study, 186 adolescents were recruited in Rio Grande do Sul, Brazil. We performed a Spearman correlation analysis to evaluate the relationships between quantitative variables. All variables that had a statistically significant correlation were included in ANOVA multiple regression models. The dependent variables in the multiple regression analyses were CDI score and total and emotional scores on the SDQ. We found that only Cognitive self-perceived rhythmicity contributed significantly to the first multiple regression with CDI as the outcome variable. The second regression with SDQ Emotional score as the outcome variable showed that female sex, age, and self-perceived affective rhythmicity contributed significantly to the model. The third regression with SDQ total score as the outcome variable showed that chronotype, self-perceived cognitive symptoms, and affective rhythmicity contributed significantly to the model. In conclusion, we found that lower self-perceived rhythmicity in cognitive factors and higher self-perceived rhythmicity in affective factors were related to presence and intensity of psychiatric and depressive symptoms.

Fluoroquinolone Derivatives in the Treatment of Mycobacterium tuberculosis Infection.

Tuberculosis (TB) is currently one of the leading causes of death due to infective agents, and the growing rate of multidrug-resistant tuberculosis (MDR TB) cases poses an emergent public health threat. Fluoroquinolones are commonly used in the treatment of both MDR TB and drug-sensitive tuberculosis patients who are intolerant to first-line antitubercular agents. Unfortunately, these drugs have mild side effects, relevant to the prolonged treatment regimens and diminished bioavailability due to binding of metal ions. Moreover, the resistance to fluoroquinolones is also on the rise, a characteristic of extensively drug-resistant TB (XDR TB). Here, we developed esters as prodrugs of the fluoroquinolones levofloxacin and ciprofloxacin, with long-chain fatty alcohols. Both the alcohols and the quinolone have previously shown antimycobacterial activity and the aim was to develop esters with improved lipophilicity and capable of delivering the free acid inside mycobacterial cells. The carboxylic acid group of fluoroquinolones is essential to the mode of action but is also responsible for many of its side effects and metal-chelating properties. The synthesis, stability in biological media, and antibacterial activity were evaluated, the latter not only against Mycobacterium tuberculosis but also against other clinically relevant bacterial species, since the parent compounds display a broad spectrum of activity. The biological results show a reduction in the antitubercular activity of the synthesized derivatives, probably due to deficient activation of the ester prodrug. Despite this, it was found that the derivatives exhibit bioactivity against other fluoroquinolone-resistant bacteria, indicating a different mode of action and suggesting that it may be worthwhile to research further modifications to the carboxylic acid group. This might lead to new compounds that are efficient against resistant strains. This idea that the compounds may act by a different mechanism of action was further supported by a brief computer investigation that demonstrated the potential lack of selectivity of the esters to the fluoroquinolone target.

Adaptation and validation of the Mood Rhythm Instrument for use in Brazilian adolescents

Objective: Adapt and validate the Mood Rhythm Instrument (MRhI), a self-reported questionnaire that assesses self-perceived rhythmicity of mood-related symptoms in adults, into a version that assesses and evaluates perceived mood-related symptoms in adolescents (MRhI-Y). Methods: Adaptation of the Brazilian Portuguese version of the MRhI for an adolescent population followed three steps: review by consultants, analysis by experts, and pilot testing through a visual analogue scale (VAS). The final questionnaire (MRhI-Y) was applied to 171 adolescents aged 12-17 years. Internal consistency was calculated using Cronbach's alpha and McDonald's omega. The psychometric properties of the MRhI-Y were evaluated using exploratory factor analysis (EFA). Results: The MRhI-Y was designed to use wording more appropriate for adolescents than that of the MRhI. Expert agreement about item quality ranged between 82 and 100%. Adolescents' VAS ratings indicated good comprehension of the items. Cronbach's alpha and McDonalds' omega coefficients were 0.71 and 0.74. The EFA resulted in a three-factor solution (affective, cognitive, and somatic). Younger adolescents (ages 12 to 13) reported lower rhythmicity scores than older groups (ages 14 to 15 and 16 to 17), even controlling for chronotype. Conclusions: The Brazilian Portuguese version of the MRhI-Y presented adequate comprehension by adolescents and good internal consistency. The MRhI-Y is a promising tool to improve our understanding of the underlying characteristics of mood fluctuation in adolescence.

Sleep disturbances, circadian activity, and nocturnal light exposure characterize high risk for and current depression in adolescence.

STUDY OBJECTIVES: Major depressive disorder (MDD) in adolescence is associated with irregularities in circadian rhythms and sleep. The characterization of such impairment may be critical to design effective interventions to prevent development of depression among adolescents. This study aimed to examine self-reported and actimetry-based circadian rhythms and sleep-wake behavior associated with current MDD and high risk (HR) for MDD among adolescents. METHODS: Ninety-six adolescents who took part in the IDEA-RiSCo study were recruited using an empirically developed depression-risk stratification method: 26 classified as low risk (LR), 31 as HR, and 39 as a current depressive episode (MDD). We collected self-report data on insomnia, chronotype, sleep schedule, sleep hygiene as well as objective data on sleep, rest-activity, and light exposure rhythms using actimetry for 10 days. RESULTS: Adolescents with MDD exhibited more severe insomnia, shorter sleep duration, higher social jetlag (SJL), lower relative amplitude (RA) of activity, and higher exposure to artificial light at night (ALAN) compared with the other groups. They also presented poorer sleep hygiene compared with the LR group. The HR group also showed higher insomnia, lower RA, higher exposure to ALAN, and higher SJL compared with the LR group. CONCLUSIONS: HR adolescents shared sleep and rhythm alterations with the MDD group, which may constitute early signs of depression, suggesting that preventive strategies targeting sleep should be examined in future studies. Furthermore, we highlight that actimetry-based parameters of motor activity (particularly RA) and light exposure are promising constructs to be explored as tools for assessment of depression in adolescence.

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic

Objective: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. Methods: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study - mostly young adult women holding university degrees. Results: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). Conclusion: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond.

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic.

OBJECTIVE: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. METHODS: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study - mostly young adult women holding university degrees. RESULTS: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). CONCLUSION: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond.

Adaptation and validation of the Mood Rhythm Instrument for use in Brazilian adolescents.

OBJECTIVE: Adapt and validate the Mood Rhythm Instrument (MRhI), a self-reported questionnaire that assesses self-perceived rhythmicity of mood-related symptoms in adults, into a version that assesses and evaluates perceived mood-related symptoms in adolescents (MRhI-Y). METHODS: Adaptation of the Brazilian Portuguese version of the MRhI for an adolescent population followed three steps: review by consultants, analysis by experts, and pilot testing through a visual analogue scale (VAS). The final questionnaire (MRhI-Y) was applied to 171 adolescents aged 12-17 years. Internal consistency was calculated using Cronbach's alpha and McDonald's omega. The psychometric properties of the MRhI-Y were evaluated using exploratory factor analysis (EFA). RESULTS: The MRhI-Y was designed to use wording more appropriate for adolescents than that of the MRhI. Expert agreement about item quality ranged between 82 and 100%. Adolescents' VAS ratings indicated good comprehension of the items. Cronbach's alpha and McDonalds' omega coefficients were 0.71 and 0.74. The EFA resulted in a three-factor solution (affective, cognitive, and somatic). Younger adolescents (ages 12 to 13) reported lower rhythmicity scores than older groups (ages 14 to 15 and 16 to 17), even controlling for chronotype. CONCLUSIONS: The Brazilian Portuguese version of the MRhI-Y presented adequate comprehension by adolescents and good internal consistency. The MRhI-Y is a promising tool to improve our understanding of the underlying characteristics of mood fluctuation in adolescence.

Mental health during the first wave of COVID-19 in Canada, the USA, Brazil and Italy.

BACKGROUND: The mental health (MH) burden on healthcare practitioners (HCPs) is emerging as a significant cost of the pandemic, although few studies have compared the MH of HCPs in different countries. METHODS: A link to an online survey was posted in the Spring of 2020 which included questions regarding perceived impact of the pandemic; current MH symptom severity and impairment was evaluated using validated scales. RESULTS: Overall, 1315 individuals (74% female, mean age: 42.9 + 16.4) in Canada, the United States, Brazil and Italy completed the survey. Nearly 26% met diagnostic thresholds for GAD and MDD; Italian respondents reported the lowest rates of disorder. Except for Canada, non-HCPs in each country reported higher symptom severity than HCPs. Amongst the HCPs, Canadian HCPs reported the highest rates of anxiety and depression as well as increases in alcohol and cannabis use, lower levels of perceived emotional support and more worry about themselves or their loved ones contracting COVID-19. CONCLUSION: Despite key infrastructural and COVID-19 mortality differences between the countries, the MH effects appeared to be quite similar. HCPs, with the exception of Canada, reported less impact on their mental health compared to the general population, suggesting resilience in the face of adversity.Key pointsRates of current mental health disorders were similar across Canada, the USA and Brazil but lower in Italy, yet much higher than pre-pandemic ratesNon-Healthcare Practitioners (HCPs) reported significantly higher severity on all MH scales in the overall sample. This was consistent within the USA, Brazil and Italy, however in Canada, HCPs reported higher anxiety, depression and stress symptom severity compared to Canadian non-HCPs.Canadian HCPs reported significantly higher anxiety and depression symptom severity than all other countriesCanadian HCPs also reported significantly greater increases in alcohol and cannabis use, lower levels of perceived emotional support and more worry about themselves or their loved ones contracting COVID-19 compared to HCPs in the other countries.

Sulfur Analogues of Tyrosine in the Development of Triazene Hybrid Compounds: A New Strategy against Melanoma.

Malignant melanoma is the major cause of death from skin cancer. Treatment of metastatic melanoma remains an enormous challenge. In this study we developed hybrid compounds and studied their potential use in malignant melanoma chemotherapy. They were designed to act by a double mechanism of action, being composed of two pharmacophores: the tyrosine sulfur analogue 4-S-cysteaminylphenol (4-S-CAP, 10), with immunomodulatory properties and specific melanocytotoxic activity, and triazene 4, with DNA alkylating properties. The design of these compounds aims to achieve selective activation by the enzyme tyrosinase overexpressed in melanoma cells. Compounds 11a-e, 13a, and 13b were found to be excellent tyrosinase substrates (0.5 min ≤ t 1/2 ≤ 3.7 min). Furthermore, derivatives 11 and 13 were evaluated for their molecular properties, hepatotoxicity, in vivo toxicity profile, and assessment of cytotoxic activity in melanoma and non-melanoma cell lines. The results were compared with those obtained for temozolomide, a triazene used in melanoma therapy. It was discovered that the hybrids are selective and effective drugs, representing a valuable model for the development of new multitarget melanoma therapy. In particular, compound 10 may be an important component for these strategies that use a metabolic pathway of melanin synthesis. Molecular hybridization of 10 with triazenes 4 renders the hybrids (11 and 13) unexpectedly devoid of hepatotoxicity while maintaining cytotoxic activity in malignant cells.

Anxiety, depression and stress during the COVID-19 pandemic: Results from a cross-sectional survey.

BACKGROUND: Multiple survey studies have demonstrated a mental health (MH) burden of COVID-19 globally. However, few studies have examined relevant risk factors for pandemic-related MH issues. METHODS: A link to an online survey was posted from April 8th - June 11th, 2020 which included questions regarding COVID-19 experience, perceived impact of the pandemic on life domains (e.g., social communication, finances), behavioural alterations (e.g., online activities, substance use), and MH treatment history. Current psychiatric symptom severity and impairment were evaluated using the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and the Perceived Stress Scale. RESULTS: Overall, 632 individuals (82% female, mean age:42.04 ± 16.56) in Canada and the United States completed the survey. While few reported contracting COVID-19 (0.5%), the impact of the pandemic was evident, with a vast majority reporting anxiety around COVID-19 infecting loved ones (88%). Almost half (43%) reported previous MH treatment and 31% met criteria for GAD, 29% for MDD and 63% reported significantly high levels of stress. Female sex, younger age and past MH treatment emerged as significant predictors of these issues(p < .01). Age-related differences in the impact of COVID-19 on life domains, substance use, and online activity were also noted. CONCLUSION: The findings from the current sample add to the growing literature suggesting negative effects of COVID-19 on MH, while highlighting specific risk factors. Age may be an important factor in predicting MH during this pandemic.

Preparation and characterization of a synthetic curcumin analog inclusion complex and preliminary evaluation of in vitro antileishmanial activity.

The aim of this work was to prepare and characterize inclusion complexes between a synthetic curcumin analog (dibenzalacetone, DBA) and beta-cyclodextrin (ß-CD); and to evaluate their in vitro antileishmanial activity. DBA was synthetized and characterized by spectroscopic methods and the inclusion complexes were obtained by kneading and lyophilization (LIO) in 1:1 and 1:2 stoichiometries. Phase solubility and dissolution assays showed a 40-fold increase in the aqueous solubility of DBA and its complete dissolution from LIO 1:1 formulation after 120 min respectively. Solid-state characterization by differential scanning calorimetry and near infrared spectroscopy demonstrated the inclusion of DBA in the ß-CD cavity at the molar ratios tested, with LIO 1:1 formulation being the most stable. Using nuclear magnetic resonance experiments, the protons inside the cavity of ß-CD were the most affected after the inclusion of DBA molecule. The cellular viability of THP-1 macrophage cells treated with plain DBA, ß-CD and DBA/CD inclusion complexes showed that the plain DBA and DBA/CD at 1:2 stoichiometry presented toxicity, while ß-CD alone and DBA/CD at 1:1 stoichiometry showed no toxicity up to 640 µg mL-1. The in vitro assay with free-living promastigotes demonstrated that plain DBA and ß-CD had IC50 of < 10 and > 320 µg mL-1 respectively, while only inclusion complexes with 1:1 stoichiometry showed antiproliferative activity with IC50 = 51.3 µg mL-1. Using the amastigote intracellular forms, there was also a difference between the plain and ß-CD complexed DBA with complexes of 1:1 and 1:2 stoichiometry presenting EC50 = 66.3 µg mL-1 and 58.9 µg mL-1 respectively. The study concluded that DBA/CD at 1:1 molar ratio has the potential to decrease the intrinsic toxicity of plain DBA towards Leishmania host cells, which may be a therapeutic advantage in the application of these compounds.

From Hemophilia to Deep Venous Thrombosis Patient Samples: How to Perform an Easy Coagulometer Validation Process According to Available Guidelines.

Validation protocols for the evaluation of coagulometers are needed to help professionals select the most suitable system for their regular laboratory routines. The objective of this study was to show how high standard protocols for the coagulometer validation process can fit into the daily laboratory routine. For this study, 45 healthy individuals and 112 patient samples were analyzed. From the patient samples, 51 were investigated for deep venous thrombosis, 27 for coagulopathy, 19 for antivitamin K therapy, and 15 for hemophilia. For the assessment, the performance of the 3 coagulometers and 1 point-of-care device was considered. One of the coagulometers was a new acquisition evaluated for precision, linearity, throughput, and carryover in the first moment, and the new coagulometer was then compared with the other well-established equipment in the laboratory. In normal plasma, coefficient of variation was ≤1.8% for total precision in screening tests and ≤3.5% for within-run precision in specific assays. For prothrombin time/international normalized ratio, no significant difference was found when comparing methods. Our study showed how to compare the capacity of a reagent in order to discriminate patients with severe hemophilia from patients with moderated hemophilia, and the κ coefficient agreement was 0.669 (95% confidence interval: 0.3-1.0; P < .001). d-dimer evaluated in patients with deep venous thrombosis and controls showed a 20% discrepancy between the methods. In our experience across Latin America, the number of laboratories that has performed this process is limited. In this study, we demonstrated how to adapt the validation process for the hemostasis laboratory routine to help the professional chose the best and more suitable option.

Validation of the English version of the Mood Rhythm Instrument.

BACKGROUND: Disruption of biological rhythms has been linked to the pathophysiology of mental disorders. However, little is known regarding the rhythmicity of mood symptoms due to the lack of validated clinical questionnaires. A better understanding of the rhythmicity of mood symptoms can help identifying individuals whose severity of mood symptoms follows an altered circadian rhythm. The objective of this study was to validate the English version of the Mood Rhythm Instrument (MRhI), a self-reported measure of self-perceived rhythmicity of mood symptoms and behaviours, in a sample of the general population from Canada. METHODS: After the translation process, the final English version of the Mood Rhythm Instrument (MRhI-English) was applied on participants recruited at McMaster University and St. Joseph's Healthcare Hamilton campuses. Individuals were also asked to answer the Reduced Morningness-Eveningness Questionnaire (rMEQ). RESULTS: Four hundred one individuals completed the English version of the MRhI and the rMEQ. The MRhI-English presented a Cronbach's alpha of 0.75. The factorial analysis grouped the MRhI-15 items in 3 factors (cognitive, affective and somatic), with affective items having a lower frequency of self-reported 24-h peaks. Comparison between sexes showed that women reported a higher frequency of daily peaks in irritability, anxiety, sadness and talking to friends, while men exhibited peaks more frequently in problem-solving, sexual arousal and motivation to exercise. CONCLUSIONS: Our findings suggest that the English version of the MRhI displayed good internal consistency. Future directions will include the use of the MRhI instrument in individuals with mood disorders, aiming to provide a better understanding of the relationship between daily patterns of mood variability and mental health outcomes.

Pyromellitic dianhydride crosslinked soluble cyclodextrin polymers: Synthesis, lopinavir release from sub-micron sized particles and anti-HIV-1 activity.

We report the synthesis of water soluble cyclodextrin (CD) polymers prepared by crosslinking pyromellitic dianhydride (PMDA) with two CD derivatives (methyl-ß-CD - MßCD and (2-hydroxy)propyl-ß-CD - HPßCD) and their evaluation as functional sub-micron sized carriers in the development of antiretroviral drug delivery systems. Using the protease inhibitor lopinavir (LPV) as model drug, LPV loaded CD polymers (pHPßCD and pMßCD) were prepared and fully characterized. The physicochemical characterization and in vitro drug release confirmed the successful synthesis of pHPßCD and pMßCD, the formation of sub-micron sized particles and a 12-14 fold increase in LPV solubility. Cytotoxicity assays indicated that both pHPßCD and pMßCD were able to improve the safety profile of LPV while the viral infectivity assay revealed a concentration independent anti-HIV-1 effect for both pHPßCD and pMßCD with a maximum percentage inhibition (MPI) of 79 and 91% respectively. After LPV loading, the antiviral profile of pHPßCD was reversed to the sigmoidal dose-response profile of LPV, while pMßCD maintained its dose-independent profile followed by a LPV mediated increase in viral inhibition. Overall, both pHPßCD and pMßCD demonstrated anti-HIV-1 activity, while drug loaded pMßCD indicated its potential as functional sub-micron sized drug delivery polymers for achieving synergistic anti-HIV activity.

Lower estimated intelligence quotient is associated with suicide attempts in pediatric bipolar disorder.

BACKGROUND: Approximately 20% of individual with pediatric bipolar disorder (PBD) have a lifetime history of suicide attempt. Some cognitive measures were associated with a suicide attempt, but no study has assessed the association of this event with the estimated intelligence quotient (IQ) in PBI. In adult Bipolar Disorder no association between IQ and suicidality was found, with different correlations between cognitive measures. There are studies in general population showing a negative correlation and others did not find any association. In Schizophrenia, IQ had a positive correlation with suicide attempt. So, the correlation between IQ and suicidality still controversial. METHODS: We recruited 63 children and adolescents younger than 18 years of age with PBD based on DSM-IV criteria from an outpatient clinic in Brazil. Manic and depressive symptoms were assessed with the YMRS and CDRS, respectively. Estimated IQ was assessed with the WISC-III. The presence or absense of suicidal attempt, clinical and demographic variables were assessed with the K-SADS-PL-W. RESULTS: Patients who attempted suicide had lower estimated IQ compared to patients who did not attempt suicide (82.72 ±â€¯18.70 vs. 101.0 ±â€¯14.36; p = 0.009). This finding remained after correction for depressive symptoms and family income (OR = 0.94; 95% CI = 0.89 - 0.99; p = 0.029). LIMITATIONS: Small sample, reverse causality could not be discarded, we only used two subscales of the WISC-III to estimate intelligence. CONCLUSION: Estimated IQ and suicide attempts were negative correlated in PBD. Future longitudinal and larger studies may confirm our findings.