Episodic disability questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

BACKGROUND: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. METHODS: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). RESULTS: Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. CONCLUSIONS: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

A Single Haplotype of IFNG Correlating With Low Circulating Levels of Interferon-γ Is Associated With Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis.

BACKGROUND: Interferon-γ (IFN-γ) plays an important role in the control of Leishmania infection. Blockade of IFN-γ signaling in mice increases lesion size and parasite load. In endemic areas of Leishmaniasis, only a fraction of the population develop the disease. This suggest that host genetics may play a role in this response. We investigated whether single nucleotide polymorphisms (SNPs) in IFNG may be associated with elevated or decrease risk in the development of cutaneous leishmaniasis (CL). METHODS: We assessed 9 SNP and cytosine-adenine (CA) repeats in IFNG by nucleotide sequencing in 647 patients with CL caused by Leishmania guyanensis and 629 controls. Circulating plasma IFN-γ levels were also assayed in 400 patients with CL and 400 controls. RESULTS: The rs2069705TT genotype is associated with elevated risk of developing CL compared with the rs2069705CC genotype (OR, 1.7; 95% CI, 1.3-2.4; P = .0008). There is a 70% chance that this genotype raises the risk of developing CL. In a dominant model, carriers of the rs2069705T allele compared with the rs2069705CC genotype showed a 50% (range, 20-100%) increased risk of developing CL (OR, 1.5; 95% CI, 1.2-2.0; P = .0004). Haplotype analysis showed 1 haplotype (H1) associated with low levels of IFN-γ presented an increased risk of 60% of developing CL (OR, 1.6; 95% CI, 1.3-1.9; P = 5 × 10-5) compared with non-H1. CONCLUSIONS: IFNG variant rs2069705 seems to be a genetic modifier of clinical outcome of Leishmania infection; individuals with the H1 haplotype, associated with low levels of IFN-γ, have a 60% risk of developing CL.

A polymorphism in the IL1B gene (rs16944 T/C) is associated with cutaneous leishmaniasis caused by Leishmania guyanensis and plasma cytokine interleukin receptor antagonist.

Nod-like Receptor Protein3 (NLRP3) inflammasome in macrophages infected with Leishmania sp. enhances the secretion of IL-1ß. Excess IL-1ß production is linked to disease severity in patients with cutaneous leishmaniasis (CL) caused by L. mexicana. Blockade of the NLRP3 inflammasome in cell cultures from skin biopsies of patients with CL caused by L. braziliensis inhibited the release of IL-1ß. We hypothesized that common single nucleotide polymorphisms in the IL1B and in its receptor antagonist IL1RN genes may be predictive of CL caused by L. guyanensis. The SNPs -511T/C (rs16944) and +3954C/T (rs1143634) of the IL1B and IL1RN VNTR (rs2234663) were assessed in 881 patients with CL and 837 healthy controls by PCR-RFLP and direct PCR respectively. Plasma cytokines levels were also assayed. The plasma levels of IL-1ß were higher in patients compared to control subjects. In contrast, increased plasma levels of IL-1Ra were observed in controls. The rs16944 C/C genotype was more common among the patients (OR = 1.5 [95%CI 1.1-2.0]; P = 0.004) and the C allele suggests susceptibility to CL (OR = 1.2 [95%CI 1.1-1.4]; P = 0.003). The rs16944 C/C genotype shows a tendency to correlate with lower levels of the IL-1Ra cytokine. Low levels of IL-1Ra cytokine and rs16944 C/C genotype seem to confer susceptibility to L. guyanensis-infection in the Amazonas.

Atrial fibrillation in a patient with Zika virus infection.

BACKGROUND: Zika virus is an emerging arbovirus of the family Flaviviridae and genus Flavivirus that until 2007 was restricted to a few cases of mild illness in Africa and Asia. CASE PRESENTATION: We report a case of atrial fibrillation disclosed during an acute Zika virus infection in a 49-year-old man. Different biological samples were analyzed for the molecular diagnosis of Zika by real-time PCR, however only the saliva specimen was positive. The patient's wife tested positive in the serum sample, although she was an asymptomatic carrier. Moreover, a complete overview of patient's biomarkers, including cytokines, chemokines, and growth-factors levels, was analyzed and compared to gender and age matching non-infected controls, as well as other Zika infected patients, considering the 95%CI of the mean values. Elevated levels of CXCL8, CCL11, CCL2, CXCL10, IL-1ß, IL-6, TNF-α, IFN-γ, IL-17, IL-1Ra, IL-4, IL-9, FGF-basic, PDGF, G-CSF, and GM-CSF were observed in the Atrial fibrillation patient, in contrast to uninfected controls. Furthermore, increased levels of CCL5, IL-1ß, TNF-α, IFN-γ, IL-9, G-CSF, and GM-CSF were observed only in the atrial fibrillation patient, when compared to other Zika patients. CONCLUSIONS: To our knowledge, this is the first description of this type of cardiac disorder in Zika patients which may be considered another atypical manifestation during Zika virus infection.

Chloroquine resistance is associated to multi-copy pvcrt-o gene in Plasmodium vivax malaria in the Brazilian Amazon.

BACKGROUND: The resistance of Plasmodium vivax to chloroquine has become an obstacle to control strategies based on the use of anti-malarials. The current study investigated the association between P. vivax CQ-resistance in vivo with copy number variation and mutations in the promoter region in pvcrt-o and pvmdr1 genes. METHODS: The study included patients with P. vivax that received supervised treatment with chloroquine and primaquine. Recurrences were actively recorded during this period. RESULTS: Among the 60 patients with P. vivax, 25 were CQ-resistant and 35 CQ-susceptible. A frequency of 7.1% of multi-copy pvcrt-o was observed in CQ-susceptible samples and 7.7% in CQ-resistant at D0 (P > 0.05) and 33.3% in CQ-resistant at DR (P < 0.05). For pvmdr1, 10.7% of the CQ-susceptible samples presented multiple copies compared to 11.1% in CQ-resistant at D0 and 0.0% in CQ-resistant at DR (P > 0.05). A deletion of 19 bp was found in 11/23 (47.6%) of the patients with CQ-susceptible P. vivax and 3/10 (23.1%) of the samples with in CQRPv at D0. At day DR, 55.5% of the samples with CQRPv had the 19 bp deletion. For the pvmdr-1 gene, was no variation in the analysed gene compared to the P. vivax reference Sal-1. CONCLUSIONS: This was the first study with 42-day clinical follow-up to evaluate the variation of the number of copies and polymorphisms in the promoter region of the pvcrt-o and pvmdr1 genes in relation to treatment outcomes. Significantly higher frequency of multi-copy pvcrt-o was found in CQRPv samples at DR compared to CQ-susceptible, indicating parasite selection of this genotype after CQ treatment and its association with CQ-resistance in vivo.

Burnout Prevalence and Associated Factors Among Brazilian Medical Students.

OBJECTIVES: This study aims to identify the prevalence of burnout and associated factors in Brazilian medical students. METHODS: In the largest medical school from Central Brazil, the Maslach Burnout Inventory-Student Survey and a socio-demographic questionnaire were adopted in this cross-sectional study. Correlations among the three dimensions of burnout were verified. RESULTS: The evaluation of 399 students revealed a frequency of 12.0% of burnout. Women had a higher rate of burnout (8.0%) than men (4.0%). The fifth period had the higher frequency of burnout (27.1%), while the seventh grade had the lower frequency (2.1%). The students showed high scores only in emotional exhaustion (63.2%). Between the dimensions "emotional exhaustion" and "disbelief" found a significant correlation. CONCLUSION: The fifth period of the Medicine course and the female gender are the most affected by burnout syndrome and therefore, the preventive actions to reduce stress among medical students should be directed mainly at these higher risk categories. The low burnout rate found in our study can attest that the PBL methodology and medical schools strategically located to meet regional demand may represent strategies for the prevention of burnout among medical students.

Identification of primary drug resistance to rifampin in Mycobacterium leprae strains from leprosy patients in Amazonas State, Brazil.

The aim of this study was to identify polymorphisms in the folp1, gyrA, and rpoB genes in leprosy patients treated in Amazonas State, Brazil. Among 197 slit-skin smear samples from untreated or relapsed patients, we found three cases of primary resistance to rifampin and one confirmed case of multidrug resistance.

HIV in MOTION: a community of practice on physical rehabilitation for and by people living with HIV and their allies.

Background: This paper describes the design, implementation, and evaluation of a community of practice (CoP), HIV in MOTION (HIM), to advance physical activity rehabilitation interventions with adults living with HIV, clinicians, researchers, and representatives from community-based organizations. We attracted a diverse audience of geographically dispersed people living with HIV, clinicians, exercise personnel, and trainees to eight HIM community of practice events that featured the clinical, research, and lived experience of people living with HIV. HIV in MOTION had (a) a domain related to physical rehabilitation, exercise, and social participation for people living with HIV; (b) a community of diverse individuals; and (c) a practice, that is, a series of sustained interactions online and offline, synchronous, and asynchronous. Our team included six diverse people living with HIV, two coordinators, and three academic researchers who planned, prepared, implemented, and evaluated each online session. To evaluate the HIV in MOTION CoP, we employed an evaluation framework composed of five criteria: Goals and Scope, Context and Structure, Process and Activities, Outcomes, and Impact. We collected quantitative and qualitative evaluative data using online evaluation, audiovisual archiving, and participant observations during the debriefing with all members of our team. Results: We widened the Goals and Scope of the HIV in MOTION CoP to include the HIV narrative of lived experiences, including autopathography, and participant storytelling. In matters of Context and Structure, we received explicit satisfaction with our governance and leadership. Also, being flexible to fit online formats was a productive strategy that made the HIV in MOTION CoP sessions agile and amenable to audiovisual archiving. Our indicators of success in Process, Activities, and Outcomes included participant retention online, elicited verbal interventions and comments in the chat room, and a rate of three repeat visits online. The indicators of success of Impact were the presence of voluntary and unscripted autopathography, the patient storytelling and how it reportedly caused changes in the participants, and the "legitimate peripheral participation" of emerging research and clinical students. In conclusion, we recommend our form of CoP for mixing the knowledge of diverse persons in this area. However, we recommend considering budget and burnout as serious challenges to sustainability.

Piloting an online telecoaching community-based exercise intervention with adults living with HIV: protocol for a mixed-methods implementation science study.

INTRODUCTION: Our aim is to evaluate the implementation of an online telecoaching community-based exercise (CBE) intervention with the goal of reducing disability and enhancing physical activity and health among adults living with HIV. METHODS AND ANALYSIS: We will conduct a prospective longitudinal mixed-methods two-phased intervention study to pilot the implementation of an online CBE intervention with ~30 adults (≥18 years) living with HIV who consider themselves safe to participate in exercise. In the intervention phase (0-6 months), participants will take part in an online CBE intervention involving thrice weekly exercise (aerobic, resistance, balance and flexibility), with supervised biweekly personal training sessions with a fitness instructor, YMCA membership providing access to online exercise classes, wireless physical activity monitor to track physical activity and monthly online educational sessions on topics related to HIV, physical activity and health. In the follow-up phase (6-12 months), participants will be encouraged to continue independent exercise thrice weekly. Quantitative assessment: Bimonthly, we will assess cardiopulmonary fitness, strength, weight, body composition and flexibility, followed by administering self-reported questionnaires to assess disability, contextual factor outcomes (mastery, engagement in care, stigma, social support), implementation factors (cost, feasibility, technology), health status and self-reported physical activity. We will conduct a segmented regression analyses to describe the change in level and trend between the intervention and follow-up phases. Qualitative assessment: We will conduct online interviews with a subsample of ~10 participants and 5 CBE stakeholders at baseline (month 0), postintervention (month 6) and end of follow-up (month 12) to explore experiences, impact and implementation factors for online CBE. Interviews will be audiorecorded and analysed using content analytical techniques. ETHICS AND DISSEMINATION: Protocol approved by the University of Toronto Research Ethics Board (Protocol # 40410). Knowledge translation will occur in the form of presentations and publications in open-access peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05006391.

Episodic Disability Questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

Background: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. Methods: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; >0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; >0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). Results: 359 participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. Conclusions: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

Kinky Sex and Deliberate Partner Negotiations: Case Studies of Canadian Transgender Men Who Have Sex with Men, Their HIV Risks, Safer Sex Practices, and Prevention Needs.

Growing research in the last two decades has begun to investigate the HIV risks and sexual health practices of transgender men, especially as a subpopulation of men who have sex with men (MSM) that likely shares certain HIV risks and sexual health practices with cisgender MSM, the sociodemographic group that continues to be at highest risk for HIV in many developed countries since the start of the epidemic. As part of our Community-Based Participatory Research project and larger strengths-based qualitative study that was dedicated to examine multiple factors that promote resilience to HIV utilizing the perspectives and lived experiences of middle-aged and older MSM, the case studies we present in this article feature the distinct insights and experiences of three HIV-negative transgender MSM from Downtown Toronto, Ontario, Canada, who participated in our one-on-one interviews. The three case studies provide not only an enlightening snapshot of some of the specific contexts, HIV risks, safer sex practices, and HIV prevention needs of transgender MSM, but also a unique opportunity to critically reflect on the potential implications of the insights and experiences that were shared by our participants, particularly for adapting and developing current and future HIV services and programs to maximally benefit transgender MSM.

"We can hardly even do it nowadays. So, what's going to happen in 5 years from now, 10 years from now?" The health and community care and support needs and preferences of older people living with HIV in Ontario, Canada: a qualitative study.

INTRODUCTION: The population of people living with HIV (PLWH) is ageing consequent to effective treatment and a steady stream of new diagnoses among older adults. PLWH experience a greater burden of age-related comorbidities and poorer social determinants of health compared to their HIV-negative peers, yet comprehensive requisites for care and support as PLWH age remain poorly understood. Preferences And Needs for Ageing Care among HIV-positive Elderly people in Ontario, Canada (PANACHE ON), explored the health and community care and social support needs and preferences of a diverse group of older PLWH (age 60+) and described life course experiences among older PLWH that shape these needs and preferences and whether they are met. METHODS: PANACHE ON was a qualitative community-based participatory research study. In-person focus groups using a semi-structured interview guide were co-facilitated by pairs of trained older PLWH from July to October 2019. Purposive sampling bolstered the inclusion of communities disproportionately affected by HIV in Ontario. Descriptive analysis was used to summarize demographic data; participatory data analysis was conducted by a subset of the research team, with transcripts double-coded and analysed using NVIVO 12 Plus. RESULTS: A total of 73 PLWH participated, 66% identified as men. The mean age was 64 years (range 55-77) and median time living with HIV was 23 years (range 2-37). The current and anticipated needs of older PLWH, many of which were only partially met, included necessities such as food and housing, mobility and sensory aids, in-home support, social and emotional support, transportation and information. Three experiences-trauma, stigma and uncertainty-intersected in the lives of many of our participants, shaping their needs for care and support, and impacting the ease with which these needs were met. CONCLUSIONS: Unmet health and social needs and limited control over the availability and accessibility of ageing-related care and support due to resource constraints or reduced capacity for self-advocacy results in anxiety about the future among older PLWH, despite their well-developed coping strategies and experience navigating systems of care. These study findings will inform the development of the first national needs assessment of older PLWH in Canada.

Providing Housing First services for an underserved population during the early wave of the COVID-19 pandemic: A qualitative study.

OBJECTIVE: We assessed the critical role of Housing First (HF) programs and frontline workers in responding to challenges faced during the first wave of the COVID-19 pandemic. METHOD: Semi-structured interviews were conducted with nine HF frontline workers from three HF programs between May 2020 and July 2020, in Toronto, Canada. Information was collected on challenges and adjustments needed to provide services to HF clients (people experiencing homelessness and mental disorders). We applied the Analytical Framework method and thematic analysis to our data. RESULTS: Inability to provide in-person support and socializing activities, barriers to appropriate mental health assessments, and limited virtual communication due to clients' lack of access to digital devices were among the most salient challenges that HF frontline workers reported during the COVID-19 pandemic. Implementing virtual support services, provision of urgent in-office or in-field support, distributing food aid, connecting clients with online healthcare services, increasing harm reduction education and referral, and meeting urgent housing needs were some of the strategies implemented by HF frontline workers to support the complex needs of their clients during the pandemic. HF frontline workers experienced workload burden, job insecurity and mental health problems (e.g. distress, worry, anxiety) as a consequence of their services during the first wave of the COVID-19 pandemic. CONCLUSION: Despite the several work-, programming- and structural-related challenges experienced by HF frontline workers when responding to the needs of their clients during the first wave of the COVID-19 pandemic, they played a critical role in meeting the communication, food, housing and health needs of their clients during the pandemic, even when it negatively affected their well-being. A more coordinated, integrated, innovative, sustainable, effective and well-funded support response is required to meet the intersecting and complex social, housing, health and financial needs of underserved and socio-economically excluded groups during and beyond health emergencies.

Differential impacts of COVID-19 and associated responses on the health, social well-being and food security of users of supportive social and health programs during the COVID-19 pandemic: A qualitative study.

The effects of the coronavirus disease-2019 (COVID-19) pandemic on the lives of underserved populations are underexplored. This study aimed to identify the impacts of the COVID-19 pandemic and associated public health responses on the health and social well-being, and food security of users of Housing First (HF) services in Toronto (Canada) during the first wave of the COVID-19 pandemic. This qualitative descriptive study was conducted from July to October 2020 in a subsample of 20 adults with a history of homelessness and serious mental disorders who were receiving HF services in Toronto. A semi-structured interview guide was used to collect narrative data regarding health and social well-being, food security and access to health, social and preventive services. A thematic analysis framework guided analyses and interpretation of the data. The COVID-19 pandemic and response measures had a variable impact on the health, social well-being and food security of participants. Around 40% of participants were minimally impacted by the COVID-19 pandemic. Conversely, among the remaining participants (impacted group), some experienced onset of new mental health problems (anxiety, stress, paranoia) or exacerbation of pre-existing mental disorders (depression, post-traumatic stress disorder and obsessive-compulsive disorder). They also struggled with isolation and loneliness and had limited leisure activities and access to food goods. The pandemic also contributed to disparities in accessing and receiving healthcare services and treatment continuity for non-COVID-19 health issues for the negatively impacted participants. Overall, most participants were able to adhere to COVID-19 public health measures and get reliable information on COVID-19 preventive measures facilitated by having access to the phone, internet and media devices and services. In conclusion, the COVID-19 pandemic and associated response measures impacted the health, social well-being, leisure and food security of people with experiences of homelessness and mental disorders who use supportive social and housing services in diverse ways.

Protective Factors That Foster Resilience to HIV/AIDS: Insights and Lived Experiences of Older Gay, Bisexual, and Other Men Who Have Sex with Men.

Since the beginning of the HIV/AIDS epidemic, gay, bisexual, and other men who have sex with men (gbMSM) have been disproportionately impacted by HIV/AIDS health disparities. Research showed that resilience to HIV/AIDS is associated with increased use of relevant health services, lower sexual health risks, and improved mental health outcomes among racially and ethnically diverse gbMSM. As the subpopulation that has historically been impacted by HIV/AIDS the longest, older gbMSM living with HIV/AIDS have inarguably exhibited resilience to HIV/AIDS the most. The qualitative study described in this paper sought to identify and examine protective factors that fostered resilience to HIV/AIDS based on the insights and lived experiences of racially and ethnically diverse, older gbMSM. Applying a community-based participatory research approach that included the meaningful involvement of older gbMSM living with HIV/AIDS in different roles (i.e., advisory committee member, collaborator, peer researcher, and participant), the study recruited and included forty-one older gbMSM living with HIV/AIDS from Ontario, Canada, in confidential, semi-structured interviews. Utilizing thematic analysis, we identified three major themes from the participant interviews as factors that fostered the resilience of older gbMSM to HIV/AIDS and helped to address HIV/AIDS health disparities: (1) established protective factors, (2) behavioral protective factors, and (3) controversial protective factors. This paper argues for the importance of valuing and capitalizing on these protective factors in the conceptualization and development of interventions, services, and programs that are dedicated to fostering resilience to HIV/AIDS.

Induced secondary structure in nanostructured films of poly(p-phenylene vinylene).

The control of emission properties in luminescent polymers such as poly(p-phenylene vinylene) (PPV) is important for various applications, and may be achieved with suitable molecular architectures in nanostructured films. This paper reports on optical properties of PPV films, using ellipsometry measurements for emitted light in the scope of the Stokes' theory. Organized PPV films obtained with the Langmuir-Blodgett (LB) method exhibited high degree of polarization for the emitted light, while cast films emitted mainly non-polarized light. From ellipsometry data, a secondary structure was inferred for poly(xylylidene tetrahydrothiophenium) chloride (PTHT), a PPV precursor, in solution, which is retained only to a small extent in the PPV cast film as thermal conversion was performed close to the glass transition temperature of PPV. On the other hand, a higher intensity of emitted light with circular polarization was observed for the LB film, which is attributed to PPV molecular secondary structure that was enhanced during the LB film deposition. Circular dichroism experiments were performed to corroborate this hypothesis. It is suggested that such a secondary structure has not been predicted in theoretical models for PPV because possible conformational changes induced in the processing steps are not taken into account.

Toll-Like Receptor-1 Single-Nucleotide Polymorphism 1805T/G Is Associated With Predisposition to Multibacillary Tuberculosis.

Tuberculosis (TB), caused by mycobacterial species of the Mycobacterium tuberculosis complex, is a serious global health issue. Brazil is among the 22 countries with the highest number of TB cases, and the state of Amazonas has the highest incidence of TB cases in the country. Toll-like receptors (TLRs) are important pattern recognition receptors of the innate immunity and play a key role in orchestrating an effective immune response. We investigated whether the single-nucleotide polymorphisms (SNPs) 1805T/G TLR1, 2258G/A TLR2, 896A/G and 1196C/T of TLR4, 745T/C TLR6, and -1237A/G and -1486A/G of TLR9 are associated with the predisposition to TB and/or bacillary load. The SNPs genotyping was performed by nucleotide sequencing in 263 TB patients and 232 healthy controls residing in the state of Amazonas. Alleles and genotypes frequencies were similar between patients and healthy individuals for most of the investigated SNPs. Stratification of the TB patients according to their bacillary load showed that the genotype 1805TT TLR1 (rs5743618) was prevalent among paucibacillary patients [odds ratio (OR) = 0.38; 95% confidence interval (CI) = 0.19-0.76; p = 0.009] while the genotype 1805TG was common among multibacillary patients (OR = 3.72; CI = 1.65-8.4; p = 0.004). Comparison of demographic characteristics of patients to controls showed that TB is strongly associated with smoking (OR = 6.55; 95% CI = 3.2-13.6; p < 0.0001); alcohol use disorder (OR = 7.14; 95% CI = 3.7-13.9; p < 0.0001); and male gender (OR = 3.66; 95% CI = 2.52-5.3; p < 0.0001). Multivariate logistic regression demonstrated that alcoholism (OR = 2.93; 95% CI = 1.05-8.16; p = 0.03) and the 1805G allele (OR = 2.75; 95% CI = 1.33-5.7; p = 0.006) are predictive variables for multibacillary TB. Altogether, we suggest that the TLR1 1805G allele may be a relevant immunogenetic factor for the epidemiology of TB together with environmental, sociodemographic, and behavioral factors.

Uterine inflammation and fertility of beef cows subjected to timed AI at different days postpartum.

The aim of this study was to evaluate the uterine health and fertility of postpartum beef cows subjected to timed AI (TAI) protocols at different days from calving. Lactating Nelore cows (Bos indicus; n = 244) were used in this study. The TAI protocols were initiated between 20 and 60 days postpartum (DPP). Cows were subjected to an estradiol-progesterone based TAI protocol. The cows were divided into three groups according to the days postpartum at the time the hormonal treatment was initiated: 1) Early (n = 64), cows between 20 and 30 DPP; 2) Middle (n = 115), cows between 31 and 45 DPP; and 3) Late (n = 65), cows between 46 and 60 DPP. At Day 0 of the protocol, endometrial cytobrush samples were collected. Slides for polymorphonuclear (PMN) cell counting were prepared and cytobrush was used for RNA extraction and analysis of relative abundance of il1, il6, il8, and tnf mRNA. Cows from the Early group had less (P < 0.05) pregnancies per AI (P/AI) than cows from Middle and Late groups; 29.7% (19/64), 45.2% (52/115), and 52.31% (34/65), respectively. Accordingly, the Early group had a greater (P < 0.05) proportion of PMN cells in the uterus than Middle and Late groups; 9.0%, 3.8%, and 2.2%, respectively. Relative abundances of il1 and il8 mRNA were greater (P < 0.05) in the Early group than Middle and Late groups. These results indicate that beef cows subjected to TAI protocols early postpartum (< 30 DPP) are less likely to become pregnant, which is associated with increased inflammation and relative abundance of mRNA for the proinflammatory cytokines il1 and il8.

An open label randomized clinical trial comparing the safety and effectiveness of one, two or three weekly pentamidine isethionate doses (seven milligrams per kilogram) in the treatment of cutaneous leishmaniasis in the Amazon Region.

BACKGROUND: American Cutaneous Leishmaniasis (ACL), a vector borne disease, is caused by various species of Leishmania and in the Amazonas, Leishmania guyanensis is predominant. The recommended drugs for treatment of cutaneous leishmaniasis (CL) in Brazil are pentavalent antimonials, pentamidine isethionate (PI) and amphotericin B. Pentamidine was initially used as metanolsulfonate or mesylate (Lomidine) at a dose of 4 mg/kg/daily, containing 2.3mg of base. This drug was withdrawn from the market in the eighties, and currently is available as PI. The PI dose required to achieve an equivalent dose of pentamidine base is 7 mg/kg, rather than the 4 mg/kg that is currently recommended in Brazil. OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of PI in a single dose, two or three doses of 7 mg/kg body weight, intramuscularly, with an interval of seven days between each dose. MATERIALS AND METHODS: This study was conducted as a controlled, randomized, open-label clinical trial for a total number of 159 patients with CL. Individuals aged 16-64 years with one to six lesions of confirmed CL based on amastigotes visualization in direct examination of Giemsa stained of dermal scraping from the border of the lesion with no previous treatment for CL and no abnormal values for liver enzymes were eligible to participate in the study. Patients with history of diabetes, cardiac, renal, and hepatic disease as well as pregnant women were excluded. Cure was defined as complete healing in the diameters of the ulcers and lesions skin six months after the end of the treatment. RESULTS: From November 2013 to December 2015, 159 patients were screened and allocated in three groups for treatment with PI: i) 53 patients were treated with a single dose intramuscularly injection of 7 mg/kg body weight; ii) 53 received two doses of 7 mg/kg within an interval of seven days; and iii) 53 were treated with three doses of 7mg/kg with an interval of seven days between each dose. In 120 patients, L. guyanensis was identified. A cure rate of 45%, 81.1% and 96.2% were observed in the first, second and third group, respectively. The cure in the three PI dose group was higher compared to the single-dose (p<0.0001) and two-dose groups (p = 0.03). No serious adverse events occurred. CONCLUSION: The present study shows that PI is a safe drug and its efficacy varied with the number of doses. The administration of PI in patients with ACL, predominantly caused by L. guyanensis, was mostly efficient in three or two doses of 7 mg/kg. TRIAL REGISTRATION: ClinicalTrials.gov NCT02919605.

Activation of adenosine A1 receptors reduces anxiety-like behavior during acute ethanol withdrawal (hangover) in mice.

Elevated signs of anxiety are observed in both humans and rodents during withdrawal from chronic as well as acute ethanol exposure, and it represents an important motivational factor for ethanol relapse. Several reports have suggested the involvement of brain adenosine receptors in different actions produced by ethanol such as motor incoordination and hypnotic effects. In addition, we have recently demonstrated that adenosine A1 receptors modulate the anxiolytic-like effect induced by ethanol in mice. In the present study, we evaluated the potential of adenosine A1 and A2A receptor agonists in reducing the anxiety-like behavior during acute ethanol withdrawal (hangover) in mice. Animals received a single intraperitoneal administration of saline or ethanol (4 g/kg) and were tested in the elevated plus maze after an interval of 0.5-24 h. The results indicated that hangover-induced anxiety was most pronounced between 12 and 18 h after ethanol administration, as indicated by a significant reduction in the exploration of the open arms of the maze. At this time interval, ethanol was completely cleared. The acute administration of 'nonanxiolytic' doses of adenosine and the selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), but not the adenosine A2A receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), at the onset of peak withdrawal (18 h), reduced this anxiogenic-like response. In addition, the effect of CCPA on the anxiety-like behavior of ethanol hangover was reversed by pretreatment with the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). These results reinforce the notion of the involvement of adenosine receptors in the anxiety-like responses and indicate the potential of adenosine A1 receptor agonists to reduce the anxiogenic effects during ethanol withdrawal.