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Background: A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil., Methods: This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources.Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE., Results: Overall, 300 patients with SLE were included (92.3% female,mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001)., Conclusion: These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country., (© 2024. The Author(s).)

The global challenge posed by the prolonged COVID-19 pandemic underscores the critical need for ongoing genomic surveillance to identify emerging variants and formulate effective public health strategies. This retrospective observational study, conducted in a reference hospital in Northeast Brazil and comprising 2116 cases, employed PCR genotyping together with epidemiological data to elucidate the impact of the Gamma variant during its emergence, revealing distinct patterns in hospitalization rates, severity of illness, and outcomes. The study emphasizes the challenges posed by the variant, particularly an increased tendency for ICU admissions and respiratory support, especially among adults aged 18 to 59 without comorbidities. Laboratory analyses further demonstrate elevated inflammatory, coagulation, and hepatic markers in the Gamma variant cohort, suggesting a more severe systemic response. Despite limitations, including a retrospective approach and single-institution data, the study underscores the importance of ongoing genomic surveillance. Overall, this research contributes valuable insights into the impact of the Gamma variant on COVID-19 dynamics, advocating for continued research and surveillance to inform effective public health strategies regarding evolving viral variants.

To evaluate aerobic capacity, strength and other physiological, nutritional, and psychological variables which may influence the performance of transgender women (TW) athletes and compare them to cisgender women (CW) and cisgender men (CM) athletes, as well as changes in TW performance over the course of a year. Prospective cohort study including three groups: TW, CW and CM volleyball athletes. Subjects will be comprehensively assessed at two different moments: baseline and after 6-12 months of adequate hormonal therapy. Evaluation will comprise clinical, medical, nutritional and psychological interviews, incremental treadmill cardiopulmonary exercise testing, hand grip strength test, vertical jump test, analysis of sleep quality (Pittsburgh Sleep Quality Index), hormonal profile, echocardiogram, analysis of resting energy expenditure, assessment of bone mass and body composition through dual-energy X-ray absorptiometry scans, and untargeted metabolomic analysis. CW and CM matched by age, body mass index and level of physical activity will undergo a similar evaluation. The assessment of the strength, aerobic capacity, haematological, nutritional and psychological status of TW using gold-standard tests will contribute to understanding the impact of oestrogen therapy on the exercise performance of these athletes and how they compare with CW and CM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the repercussions of the COVID-19 pandemic on lymphedema patients from an endemic area of lymphatic filariasis. Methods: The study descriptive compared sociodemographic and clinical aspects, risk of falling and quality of life, prior and during the COVID-19 pandemic in 28 lymphedema patients, older than 18 years old and under investigation of filarial infection. For the evaluation of functional mobility, the Time Up and Go test and The Medical Outcome Study Short Form-36 Health for quality of life, was used. Results: An increase in interdigital and dermal lesions, a higher frequency of acute dermatolymphangioadenitis crises and risk of falling, worsening of quality of life in the domains of physical functioning, general health, vitality, and mental health during the pandemic was observed. Conclusion: Our findings of clinical worsening and quality of life of patients during the COVID-19 pandemic indicate the need to reinforce the goal of the Lymphatic Filariasis Program regarding the follow-up of these patients in the actions of the Global Program for the Elimination of Lymphatic Filariasis, due to the discontinuity in the care during the pandemic., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Aquino, Aguiar-Santos, Rocha, Coutinho, Nascimento, Moretti, Silva, Lima, Bonfim and Medeiros.)

Background: The COVID-19 pandemic has caused major disruptions in all aspects of daily functioning, from school and work to interactions with friends and family. The Functioning Assessment Short Test (FAST) is an interviewer-administered scale validated in the psychiatric sample with no previous study assessing its validity and reliability in a digital format. Thus, we aimed to analyse the psychometric properties of the digital version of the FAST and understand the implications of COVID-19 and restrictive measures on functioning., Methods: Data were collected using an online survey. The psychometric properties of the digital FAST were assessed by confirmatory factor analysis, Cronbach's alpha, and discriminant functional by cluster analysis in a community sample., Results: Out of the total sample, 2,543 (84.1%) were female, and the mean (SD) age was 34.28 (12.46) years. The digital FAST retained the six factors structure observed in the original version, with Cronbach's alpha above 0.9. In addition, we showed evidence of discriminant validity by differentiating three clusters of psychosocial functioning. Clinical and demographic differences between groups explained, in part, the heterogeneity of functioning, thus providing support for the construct validity of the instrument., Conclusion: The digital FAST is a simple and easy-to-understand instrument that provides a multidimensional assessment of functioning without the need for an interviewer. Furthermore, our findings may help to better understand the psychosocial implications of the pandemic and the importance of planning specific interventions to rehabilitee the affected group., Competing Interests: E.V. has received grants and served as a consultant, advisor or CME speaker unrelated to this work for the following entities: AB-Biotics, Abbvie, Angelini, Dainippon Sumitomo Pharma, Ferrer, GH Research, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda. The other authors do not declare any conflict of interest related to this manuscript., (© 2022 Serafim et al.)

Background: Subjects with bipolar disorder (BD) show heterogeneous cognitive profile and that not necessarily the disease will lead to unfavorable clinical outcomes. We aimed to identify clinical markers of severity among cognitive clusters in individuals with BD through data-driven methods., Methods: We recruited 167 outpatients with BD and 100 unaffected volunteers from Brazil and Spain that underwent a neuropsychological assessment. Cognitive functions assessed were inhibitory control, processing speed, cognitive flexibility, verbal fluency, working memory, short- and long-term verbal memory. We performed hierarchical cluster analysis and discriminant function analysis to determine and confirm cognitive clusters, respectively. Then, we used classification and regression tree (CART) algorithm to determine clinical and sociodemographic variables of the previously defined cognitive clusters., Results: We identified three neuropsychological subgroups in individuals with BD: intact (35.3%), selectively impaired (34.7%), and severely impaired individuals (29.9%). The most important predictors of cognitive subgroups were years of education, the number of hospitalizations, and age, respectively. The model with CART algorithm showed sensitivity 45.8%, specificity 78.4%, balanced accuracy 62.1%, and the area under the ROC curve was 0.61. Of 10 attributes included in the model, only three variables were able to separate cognitive clusters in BD individuals: years of education, number of hospitalizations, and age., Conclusion: These results corroborate with recent findings of neuropsychological heterogeneity in BD, and suggest an overlapping between premorbid and morbid aspects that influence distinct cognitive courses of the disease.

Background: The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the importance of implementing strategic management that prioritizes the safety of frontline nurse professionals. In this sense, this research was aimed at identifying factors associated with the illness of nursing professionals caused by COVID-19 according to socio-demographic, clinical, and labor variables., Methods: A cross-sectional study was conducted in three Brazilian university hospitals with 859 nursing professionals, which include nurses, technicians, and nursing assistants, between November 2020 and February 2021. We present data using absolute and relative frequency. We used Chi-square test for hypothesis testing and multiple logistic regression for predictive analysis and chances of occurrence., Results: The rate of nursing professionals affected by COVID-19 was 41.8%, and the factors associated with contamination were the number of people in the same household with COVID-19 and obesity. Being a nurse was a protective factor when the entire nursing team was considered. The model is significant, and its variables represent 56.61% of the occurrence of COVID-19 in nursing professionals., Conclusion: Obesity and living in the same household as other people affected by COVID-19 increases the risk of contamination by this new coronavirus., Competing Interests: The authors report no biomedical financial interests or potential conflicts of interest., (© 2022 Occupational Safety and Health Research Institute.)

Trypanosoma cruzi , the etiological agent of Chagas disease, exhibits extensive inter- and intrastrain genetic diversity. As we have previously described, there are some genetic differences between the parental G strain and its clone D11, which was isolated by the limiting dilution method and infection of cultured mammalian cells. Electrophoretic karyotyping and Southern blot hybridization of chromosomal bands with specific markers revealed chromosome length polymorphisms of small size with additional chromosomal bands in clone D11 and the maintenance of large syntenic groups. Both G strain and clone D11 belong to the T. cruzi lineage TcI. Here, we designed intraspecific array-based comparative genomic hybridization (aCGH) to identify chromosomal regions harboring copy-number variations between clone D11 and the G strain. DNA losses were more extensive than DNA gains in clone D11. Most alterations were flanked by repeated sequences from multigene families that could be involved in the duplication and deletion events. Several rearrangements were detected by chromoblot hybridization and confirmed by aCGH. We have integrated the information of genomic sequence data obtained by aCGH to the electrophoretic karyotype, allowing the reconstruction of possible recombination events that could have generated the karyotype of clone D11. These rearrangements may be explained by unequal crossing over between sister or homologous chromatids mediated by flanking repeated sequences and unequal homologous recombination via break-induced replication. The genomic changes detected by aCGH suggest the presence of a dynamic genome that responds to environmental stress by varying the number of gene copies and generating segmental aneuploidy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cortez, Lima, Reis-Cunha, Bartholomeu, Villacis, Rogatto, Costa-Martins, Marchiano, do Carmo, da Silveira and Marini.)

Purpose: Depression and impairment of quality of life (QoL) reduce the survival of individual on hemodialysis (HD). However, few studies evaluated the impact of these conditions on the survival of older patients undergoing HD., Methods: A retrospective cohort study was performed including patients aged ≥ 60 years on HD in Recife, Brazil, assessed in 2013 and monitored until 2017. Depression was evaluated with the Mini-International Neuropsychiatric Interview and QoL with the Control, Autonomy, Self-realization, and Pleasure Questionnaire (CASP-16). Survival differences according to the depression and QoL status were measured by Kaplan-Meier analysis and Cox regression. Death Certificates were analyzed to assess the cause of death., Results: A total of 171 patients were included (mean age 68.7 ± 6.9 years). The mean follow-up time was 3 years (maximum 4.5 years) and there were 98 deaths (57.3% of the sample). In a multivariate model that included depression and QoL, only QoL impairment was associated with a higher risk of death (HR 1.62, p = 0.035). Among CASP domains, only "Control" was associated with survival (HR 0.90, p = 0.014). Depression was unrelated to the cause of death, but there was a trend for death by endocrine diseases if QoL was impaired (p = 0.057)., Conclusion: QoL impairment is a key predictor of prognosis in older patients on HD and may be more important than depression. It is important that teams dealing with this population include in protocols an assessment of QoL, in order to offer a range of care according to the needs of these patients.

Background: Anterior cruciate ligament (ACL) repair is increasing in frequency in younger children. Recognition of the normal development of the intercondylar notch is important for successful ACL graft placement, allowing surgeons to better understand the anatomy and risk factors related to ACL tears and its reconstruction. The purpose of this study was to compile normative data on the intercondylar notch in the pediatric population with magnetic resonance imaging (MRI), emphasizing the differences between males and females., Methods: In this retrospective study, musculoskeletal radiologists evaluated intercondylar notch width, bicondylar distance and notch width index (NWI). A total of 253 MRI examinations (130 males and 123 females between six and 18 years of age) were included. The association between measurements, sex and age was considered. Linear and fractional polynomial regression models were used to evaluate the relationships between measurements., Results: Intercondylar notch width increased up to 10 years of age in females and 11 years of age in males, with relative stabilization up to 13 years in girls and 14 years in boys and a slight reduction in values at subsequent ages. Bicondylar distance showed significant progressive growth with age in both sexes. NWI showed a discrete and homogenous reduction with age in both sexes., Conclusion: Intercondylar notch width interrupts its growth around 10-11 years of age, with relative stabilization up to 13-14 years and a slight reduction in dimensions in subsequent ages. This growth pattern resembles the development of the ACL area observed in recent studies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Depression is highly prevalent in hemodialysis patients, but few studies have evaluated older hemodialysis patients. The aim of this study was to evaluate the prevalence of depression, its associated factors and its impact on quality of life in an older population on hemodialysis., Methods: This was a cross-sectional study including 173 hemodialysis patients aged 60 years or older in Recife, Brazil. Depression was evaluated using the Mini-International Neuropsychiatric Interview when depressive symptoms (according to the 5-item Geriatric Depression Scale) were present. Quality of life was assessed with the Control, Autonomy, Self-realization and Pleasure Questionnaire (CASP-16). Data were also collected on sociodemographic, laboratory (albumin, parathormone, hemoglobin, and phosphorus) and dialysis (dialysis vintage, vascular access and hemodialysis adequacy) characteristics., Results: Depression was present in 22.5% of the sample. Depressed patients presented low CASP-16 quality of life scores (31.6 vs. 24.2, p < 0.001), twice the odds of albumin levels < 3.8 g/dL (OR 2.36; 95%CI 1.10-5.07; p = 0.027) and higher parathormone levels (OR 1.06; 95%CI 1.00-1.13; p = 0.05)., Conclusion: Older hemodialysis patients have a high prevalence of depression. Depressed patients presented poor quality of life, lower serum albumin and higher parathormone levels. Teams dealing with older hemodialysis patients should include depression and quality of life assessments in care protocols.

Background: Emotional memory is a critical amygdala-dependent cognitive function characterized by enhanced memory for emotional events coupled with retrograde amnesia. Our study aims to assess the influence of bipolar disorder (BD), trauma, and the number of mood episodes on emotional memory., Methods: 53 subjects (33 euthymic patients with BD and 20 healthy controls) answered a clinical assessment, childhood trauma questionnaire (CTQ), and an emotional memory test composed of lists of nouns, including neutral words, one emotional (E), one preceding (E-1) and one following word (E + 1). We assessed for the influence of type, position, diagnosis, trauma, and number of mood episodes in word recall using generalized estimating equations., Results: Controlling for neutral words, BD had a higher recall for E-1 (p = 0.038) and a trend for a higher recall of E (p = 0.055). There was no difference between patients with and without trauma. Patients with BD who suffered multiple mood episodes had a higher recall of E compared to patients with fewer episodes (p = 0.016)., Limitations: Cross-sectional design and small sample size., Conclusion: Our results indicate dysfunction in emotional memory in patients with BD, particularly after multiple mood episodes. While we expected an impaired emotional memory, patients with BD showed an increased recall for emotional stimuli and events preceding them. Childhood trauma does not seem to interfere with emotional memory changes in patients with BD. Emotional memory enhancement seems to be a promising marker of progression in BD., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: The aim of this study was to retrospectively compile normative data on the anterior cruciate ligament (ACL) in the paediatric population with magnetic resonance imaging, emphasizing the differences between men and women., Methods: In this retrospective study, musculoskeletal radiologists evaluated length, area, coronal and sagittal inclination of the ACL and inclination of the intercondylar notch. A total of 253 MR examinations (130 males and 123 females between 6 and 18 years of age) were included. The association between measurements, sex and age was considered. Linear and fractional polynomial regression models were used to evaluate the relationships between measurements., Results: ACL length showed significant progressive growth (p < 0.001) with age in men and women, without characterization of growth peaks. ACL area in women showed more pronounced growth up to 11 years, stabilized from 11 to 14 years and then sustained a slight reduction. In men, ACL area showed more pronounced growth up to 12 years, stabilized from 12 to 15 years and then sustained slight reduction. Coronal and sagittal inclination of the ACL showed a significant progressive increase (p < 0.001) with age in both sexes, progressively verticalizing. The intercondylar roof inclination angle showed significant progressive reduction (p < 0.001) with age in both sexes., Conclusion: The area of the ACL does not accompany skeletal maturation, interrupting its growth around 11-12 years. Progressive verticalization of the ACL as well as of the intercondylar notch roof in the evaluated ages was also observed. The clinical relevance of this study is that the ACL presents different angular and morphologic changes during growth in the paediatric population. Since ACL repair is now being performed on younger children, recognition of the normal developmental changes of the ACL is of utmost importance for successful ACL graft placement., Level of Evidence: III.

The HIV-1 virus (human immunodeficiency virus) affects 36.9 million people worldwide, with approximately 900000 deaths in 2017. The virus carrier can develop severe immunodeficiency since CD4 + T lymphocytes are the main target, leading to acquired immunodeficiency syndrome (AIDS). Despite advances in pharmacological treatment, it is still difficult to eliminate latent reservoirs, becoming one of the main obstacles for viral eradication. The CRISPR- (clustered regularly interspaced short palindromic repeat-) Cas system is a genome-editing method which uses a guide RNA, a complementary sequence to the interested site, recruiting a nuclease that can break the viral or the host cell genetic material. From this double-stranded break, cellular repair mechanisms are activated being able to generate deletions, insertions, or substitutions, in order to inactivate specific gene loci, leading to loss of function. The objective of this minireview is to synthesize the current knowledge on the application of CRISPR-Cas-based gene therapy for HIV-1. The strategies encompass all steps of the viral infection cycle, from inhibition of cell invasion, through viral replication and integration inhibition, to excision of the latent provirus. Off-target effects and ethical implications were also discussed to evaluate the safety of the approach and viability of its application in humans, respectively. Although preclinical and clinical tests are still needed, the recent results establish an exciting possibility of applying this technology for prophylaxis and treatment of HIV-1., Competing Interests: The authors have declared that no conflict of interest exists.

Purpose: Enteropathogens are frequently associated with diarrheal disease. Knowledge of their etiology and epidemiology is essential for the prevention and control of the sickness. This study describes the microbiological and epidemiological features of diarrheal disease in 197 symptomatic and 223 asymptomatic under-five-year-old children from southeastern Brazil, between January 2015 and September 2016., Methods: Isolation of Escherichia coli, Salmonella, Shigella and Campylobacter was realized by culture. E. coli strains were screened by multiplex PCR, PFGE and O:H serotyping. Antimicrobial susceptibility testing was also performed., Results: Most of the 127 enteropathogens isolated were diarrheagenic E. coli (96.1 %), with predominance of several serotypes of enteropathogenic E. coli (EPEC) and enteroaggregative E. coli (EAEC). Age, sex, rotavirus vaccination, recent use of antibiotics and previous contact with pets, were factors that revealed no significant effects on the probability of infection by the predominant pathogens. Even so, higher incomes could be related to a lesser chance of testing positive for EPEC. Evidence of possible EAEC clonal spread was detected, as well as genetic similarity among strains from both symptomatic and asymptomatic children. Resistance to antimicrobial agents was more pronounced among EAEC than EPEC., Conclusion: The occurrence of genetically similar diarrheagenic E. coli in both groups of children, likewise resistant to these agents, underscores the importance of establishing strategies for the prevention of outbreaks, especially among low-income households.

Maltreatments in childhood may have implications for neurodevelopment that could remain throughout life. Childhood trauma seems to be associated with the onset of bipolar disorder (BD), and its occurrence might accentuate the overall disease impairments related to cognitive deficits in BD. We aimed to evaluate the effects of a history of childhood trauma to estimated intellectual functioning (IQ) of individuals with BD. We included 72 subjects with BD during euthymia. Participants underwent a clinical interview and were assessed through the Childhood Trauma Questionnaire (CTQ) and Wechsler Abbreviated Scale of Intelligence (WASI). Most prevalent trauma subtypes were emotional abuse and neglect (54.1%). A linear regression model that included perceived childhood trauma, family history of severe mental disorders, age at diagnosis and psychotic symptoms during the first episode as main factors showed that only childhood trauma had a significant effect in predicting estimated IQ. Therefore, the history of childhood trauma in individuals with BD may play a role in intellectual development, suggesting that adversities during development result in decreased general cognitive abilities. These results reinforce the need to promote early interventions to protect childhood and to promote the well-being of children, contributing to the growth of healthy adults., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Importance: Congenital Zika syndrome virus infection is said to interfere in children's development., Objective: evaluate gross motor trajectories and the frequency of cerebral palsy in children with congenital Zika syndrome., Design: Cohort study applying the Alberta Infant Motor Scale (AIMS) and the Bayley III Scales in infants from 6 to 18 months of age., Setting: The SARAH network, Rio de Janeiro., Participants: Thirty-nine infants whose diagnoses were established through clinical history, serology tests, and neuroimaging findings. Main outcomes and measures: Congenital Zika syndrome is associated with severe motor delays and is a risk factor to the diagnosis of cerebral palsy., Results: The Alberta Infant Motor Scale mean raw score at 6 months was 9.74 (SD 4.80) or equivalent to 2 to 3 months of motor developmental age. At the age of 12 months, 14.13 (SD 11.90), corresponding to 3 to 4 months of motor development age; the Bayley III Scales results correlated to the Alberta Infant Motor Scale ( P < .001) at this age. At 18 months, 15.77 (SD 13.80) or a motor development equivalent to 4 to 5 months of age. Thirty-five of 39 children (89.7%) met criteria for the diagnosis of cerebral palsy. Conclusions and relevance: Gross motor development marginally progresses from 6 to 18 months of age. These individuals also displayed a high frequency of cerebral palsy.

Introduction and Hypothesis: Our aim was to validate the Brazilian Portuguese version of the International Federation of Gynecology and Obstetrics (FIGO) Assessment Scoring System (FASS) to identify and quantify signs and symptoms related to pelvic floor dysfunction., Methods: One hundred and seventy-nine women aged 18-82 (47.68 ± 14.42) years participated in this validation study. Collected data included a sociodemographic and clinical questionnaire, application of the FASS, and physical examination using the Pelvic Prgan Prolapse Quantification (POP-Q) system. The translation and cross-cultural adaptation were performed following the international methodology. The psychometric properties tested were criterion validity, construct validity, stability, and reliability. For this purpose, the comparison with POP-Q findings and between symptomatic and asymptomatic patients, test-retest and internal consistency (Cronbach's alpha) were used, respectively. The intraclass correlation coefficient (ICC) was calculated to assess the level of agreement between evaluations (inter- and intraobservers). P < 0.05 was considered statistically significant., Results: The calculated Cronbach's alpha coefficient was 0.76, indicating strong reliability for the validation sample. Symptomatic women had different scores on all FASS items as well as total score when compared with asymptomatic women (p < 0.001). Intraobserver coefficient ranged from 0.91 (urinary symptoms) to 0.98 (FASS total score), indicating excellent concordance level in all items. Interobserver coefficient ranged from 0.47 (intestinal symptoms) to 0.90 (FASS total score), indicating moderate to excellent correlation., Conclusions: The psychometric properties tested in the FASS Portuguese version proved to be a valid and reliable for evaluating signs and symptoms related to pelvic floor function in Brazilian women.

Nutritional recovery of early malnutrition with a soybean diet reduces liver glycogen stores in the fed state and produces liver insulin resistance. We investigated whether nutritional recovery on a soybean flour diet alters hepatic gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation. Male rats from mothers that were fed either 17% (C) or 6% (L) protein during pregnancy and lactation were maintained on a 17% casein (CC, n = 16 and LC, n = 17), 17% soybean flour (CS, n = 10 and LS, n = 10), or 6% casein (LL, n = 10) diet after weaning. The soybean diet reduced basal serum glucose (soybean diet, 5.6 ± 0.6 mmol/L vs. casein diet, 6.2 ± 0.6 mmol/L; p < 0.05) but increased alanine aminotransferase mRNA/GAPDH (soybean diet, 0.062 ± 0.038 vs. casein diet, 0.024 ± 0.011; p < 0.01), phosphoenolpyruvate carboxykinase mRNA/GAPDH (soybean diet, 1.53 ± 0.52 vs. casein diet, 0.95 ± 0.43; p < 0.05), and glycerokinase protein content (soybean diet, 0.86 ± 0.08 vs. casein diet, 0.75 ± 0.11; p < 0.05). The serum glucose concentration (recovered groups, 5.6 ± 0.5 mmol/L vs. control groups, 6.2 ± 0.7 mmol/L; p < 0.05) and phosphoenolpyruvate carboxykinase activity (recovered groups, 2.8 ± 0.6 μU/mg vs. control groups, 3.6 ± 0.6 μU/mg; p < 0.05) were decreased in rats subjected to protein restriction in early life. The glucose area under the curve during the pyruvate tolerance test did not differ among groups, whereas glucose area under the curve after glucagon infusion was reduced by early malnutrition (recovered groups, 4210 ± 572 mg/dL·40 min vs. control groups, 4493 ± 688 mg/dL·40 min; p < 0.001) and by the soybean diet (soybean diet, 3995 ± 500 mg/dL·40 min vs. casein diet, 4686 ± 576 mg/dL·40 min; p < 0.05). Thus, the soybean diet impaired the response to glucagon but did not alter gluconeogenesis.

Purpose: Our aim was to evaluate the effects of deep breathing exercises in subjects with bipolar disorder., Design and Methods: This was an open-label, uncontrolled clinical trial with three assessments: preintervention, postintervention, and follow-up., Findings: The Hamilton Anxiety Rating Scale, BECK-A, Hamilton Depression Rating Scale, and Young Mania Rating Scale had significant preintervention, postintervention, and follow-up differences. The results indicated that the deep breathing protocol was effective in reducing anxiety levels in patients with bipolar disorder. The deep breathing protocol has no negative side effects and might be applied to decrease anxiety symptoms in individuals with bipolar disorder., Practice Implications: The results provide direction for providing quality care that reduces anxiety levels in patients with bipolar disorder., (© 2018 Wiley Periodicals, Inc.)

The published version of this article, unfortunately, contains an error in that Fig. 2 shows the same study as Fig. 3. The correct Fig. 2 is shown below.

The mevalonate pathway is an essential part of isoprenoid biosynthesis leading to production of a diverse class of >30,000 biomolecules including cholesterol, heme, and all steroid hormones. In trypanosomatids, the mevalonate pathway also generates dolichols, which play an essential role in construction of glycosylphosphatidylinositol (GPI) molecules that anchor variable surface proteins (VSGs) to the plasma membrane. Isoprenoid biosynthesis involves one of the most highly regulated enzymes in nature, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), which catalyzes the conversion of HMG-CoA to mevalonic acid. The enzyme mevalonate kinase (MVK) subsequently converts mevalonic acid to 5-phosphomevalonic acid. Trypanosoma evansi is a flagellate protozoan parasite that causes the disease "Surra" in domesticated large mammals, with great economic impact. T. evansi has only a trypomastigote bloodstream form and requires constant modification of the variant surface glycoprotein (VSG) coat for protection against the host immune system. We identified MVK of T. evansi (termed TeMVK) and performed a preliminary characterization at molecular, biochemical, and cellular levels. TeMVK from parasite extract displayed molecular weight ~36 kDa, colocalized with aldolase (a glycosomal marker enzyme) in glycosomes, and is structurally similar to Leishmania major MVK. Interestingly, the active form of TeMVK is the tetrameric oligomer form, in contrast to other MVKs in which the dimeric form is active. Despite lacking organized mitochondria, T. evansi synthesizes both HMGCR transcripts and protein. Both MVK and HMGCR are expressed in T. evansi during the course of infection in animals, and therefore are potential targets for therapeutic drug design.

Purpose: To evaluate the role of miR-124a in the regulation of genes involved in insulin exocytosis and its effects on the kinetics of insulin secretion in pancreatic islets from pregnant rats submitted to a low-protein diet., Methods: Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. Kinetics of the glucose-induced insulin release and measurement of [Ca 2+ ] i in pancreatic islets were assessed by standard protocols. The miR-124a expression and gene transcriptions from pancreatic islets were determined by real-time polymerase chain reaction., Results: In islets from LPP rats, the first phase of insulin release was abrogated. The AUC [Ca 2+ ] i from the LPP group was lower compared with the other groups. miR-124a expression was reduced by a low-protein diet. SNAP-25 mRNA, protein expression, and Rab3A protein content were lower in the LPP rats than in CP rats. Syntaxin 1A and Kir6.2 mRNA levels were decreased in islets from low-protein rats compared with control rats, whereas their protein content was reduced in islets from pregnant rats., Conclusions: Loss of biphasic insulin secretion in islets from LPP rats appears to have resulted from reduced [Ca 2+ ] i due, at least in part, to Kir6.2 underexpression and from the changes in exocytotic elements that are influenced either directly or indirectly by miR-124a.

The effect of physical activity on the immune system is still poorly understood in cases of systemic lupus erythematosus (SLE). Therefore, our aim was to investigate differences in the serum levels of cytokines (IL-2, IL-5, IL-6, IL-8, IL-10 and TNF-α) and the numbers of CD11b + and CXCR2 + neutrophils and lymphocytes in women with SLE undergoing drug treatment, without ( n = 9) or with ( n = 5) 4 months of kinesiotherapy. Parameters related to functional capacity were also analyzed. In the case of the patients who were not submitted to kinesiotherapy, there were reductions in the levels of IL-5, IL-6 and IL-10, and an increase in the number of CD11b + leukocytes, in addition to an increase in abdominal circumference after the monitoring time. Patients submitted to kinesiotherapy did not present changes in serum cytokines or in the numbers of CD11b + and CXCR2 + neutrophils and lymphocytes, but there were increases of flexibility and strength, as well as a reduction in pain sensation after the monitoring time. In conclusion, kinesiotherapy was able to increase flexibility and reduce pain in SLE patients without influencing immune parameters.

There is global concern about acid rain and other pollution which is caused by the consumption of oil. By decreasing sulfur content in the oil, we can reduce unwanted emissions and acid rain. Shale was used which is a solid waste generated in the pyrolysis of shale, impregnated with Zn as an adsorbent which removes sulfur present in fuels from the hexane/toluene model solution. An influence of the agitation time (60-180 min), temperature (25-35 °C), adsorbent mass (0.1-0.25 g), and initial sulfur concentration (100-250 ppm) factorial 24 with three central points totaling 19 experiments was applied to investigate the effect of the variables on the efficiency of sulfur removal in fuels. The values of the parameters tested for maximum sulfur removal were obtained as follows: contact time = 180 min, temperature = 35 °C, adsorbent mass = 0.25 g, and initial sulfur concentration = 100 ppm. The mathematical model proposed with R 2 99.97% satisfied the experimental data. This may provide a theoretical basis for new research and alternative uses for tailings of schist industrialization in order to evaluate its potential.

Introduction: In Brazil, there is no valid instrument to measure subjective cognitive dysfunction in bipolar disorder. The present study analyzed the psychometric properties of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Brazilian bipolar patients. We further investigated the relationship between the COBRA, objective cognitive measures, and illness course variables., Methods: The total sample (N=150) included 85 bipolar disorder patients and 65 healthy controls. The psychometric properties of the COBRA (e.g., internal consistency, concurrent validity, discriminative validity, factor analyses, ROC curve, and feasibility) were analyzed., Results: The COBRA showed a one-factor structure with very high internal consistency (Cronbach's alpha=0.890). Concurrent validity was indicated by a strong correlation with the cognitive domain of the FAST (r=0.811, p<0.001). Bipolar patients experienced greater cognitive complaints (mean=14.69; standard deviation [SD]=10.03) than healthy controls (mean=6.78; SD=5.49; p<0.001), suggesting discriminative validity of the instrument. No significant correlations were found between the COBRA and objective cognitive measures. Furthermore, higher COBRA scores were associated with residual depressive (r=0.448; p<0.001) and manic (r=0.376; p<0.001) symptoms, number of depressive episodes (r=0.306; p=0.011), number of total episodes (r=0.256; p=0.038), and suicide attempts (r=0.356; p=0.003)., Conclusion: The COBRA is a valid instrument to assess cognitive complaints, and the combined use of subjective-objective cognitive measures enables the correct identification of cognitive dysfunctions in bipolar disorder.

Considering the limited number of available lung donors, lung bioengineering using whole lung scaffolds has been proposed as an alternative approach to obtain lungs suitable for transplantation. However, some decellularization protocols can cause alterations on the structure, composition, or mechanical properties of the lung extracellular matrix. Therefore, the aim of this study was to compare the acellular lung mechanical properties when using two different routes through the trachea and pulmonary artery for the decellularization process. This study was performed by using the lungs excised from 30 healthy male C57BL/6 mice, which were divided into 3 groups: tracheal decellularization (TDG), perfusion decellularization (PDG), and control groups (CG). Both decellularized groups were subjected to decellularization protocol with a solution of 1% sodium dodecyl sulfate. The behaviour of mechanical properties of the acellular lungs was measured after decellularization process. Static (Est) and dynamic (Edyn) elastances were obtained by the end-inspiratory occlusion method. TDG and PDG showed reduced Est and Edyn elastances after lung decellularization. Scanning electron microscopy showed no structural changes after lung decellularization of the TDG and PDG. In conclusion, was demonstrated that there is no significant difference in the behaviour of mechanical properties and extracellular matrix of the decellularized lungs by using two different routes through the trachea and pulmonary artery.

Duraplasty is necessary in nearly 30% of all neurological surgeries. Different tissues and materials have been evaluated in dura mater repair or as dural substitutes in neurosurgery. The aim was to evaluate the biocompatibility of the bacterial cellulose (BC) membranes, produced from sugarcane molasses, for dural defect repair in rats. Forty adults males Wistar rats divided into two groups: a control (ePTFE) and an experimental (BC). Bilateral frontoparietal craniectomy was performed, and a dural defect was created. The arachnoid underlying defect was disrupted with a narrow hook. The animals were observed for 120 days. There were no cases of infection, cerebrospinal fluid fistulae, delayed hemorrhages, behavior disturbances, seizures and palsies. The BC membrane showed to have suitable biocompatibility properties, was not induced immune reaction, nor chronic inflammatory response and absence of neurotoxicity signals.

Mevalonate kinase (MVK) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. MVK is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. During the course of T. cruzi MVK characterization, we found that, in addition to glycosomes, this enzyme may be secreted and modulate cell invasion. To evaluate the role of TcMVK in parasite-host cell interactions, TcMVK recombinant protein was produced and anti-TcMVK antibodies were raised in mice. TcMVK protein was detected in the supernatant of cultures of metacyclic trypomastigotes (MTs) and extracellular amastigotes (EAs) by Western blot analysis, confirming its secretion into extracellular medium. Recombinant TcMVK bound in a non-saturable dose-dependent manner to HeLa cells and positively modulated internalization of T. cruzi EAs but inhibited invasion by MTs. In HeLa cells, TcMVK induced phosphorylation of MAPK pathway components and proteins related to actin cytoskeleton modifications. We hypothesized that TcMVK is a bifunctional enzyme that in addition to playing a classical role in isoprenoid synthesis in glycosomes, it is secreted and may modulate host cell signaling required for T. cruzi invasion.

Trans-sialidase (TS) is a polymorphic protein superfamily described in members of the protozoan genus Trypanosoma. Of the eight TS groups recently described, TS group I proteins (some of which have catalytic activity) are present in the distantly related Trypanosoma brucei and Trypanosoma cruzi phylogenetic clades, whereas other TS groups have only been described in some species belonging to the T. cruzi clade. In the present study we analyzed the repertoire, distribution and phylogenetic relationships of TS genes among species of the T. cruzi clade based on sequence similarity, multiple sequence alignment and tree-reconstruction approaches using TS sequences obtained with the aid of PCR-based strategies or retrieved from genome databases. We included the following representative isolates of the T. cruzi clade from South America: T. cruzi, T. cruzi Tcbat, Trypanosoma cruzi marinkellei, Trypanosoma dionisii, Trypanosoma rangeli and Trypanosoma conorhini. The cloned sequences encoded conserved TS protein motifs Asp-box and VTVxNVxLYNR but lacked the FRIP motif (conserved in TS group I). The T. conorhini sequences were the most divergent. The hybridization patterns of TS probes with chromosomal bands confirmed the abundance of these sequences in species in the T. cruzi clade. Divergence and relationship analysis placed most of the TS sequences in the groups defined in T. cruzi. Further examination of members of TS group II, which includes T. cruzi surface glycoproteins implicated in host cell attachment and invasion, showed that sequences of T. cruzi Tcbat grouped with those of T. cruzi genotype TcI. Our analysis indicates that different members of the T. cruzi clade, with different vertebrate hosts, vectors and pathogenicity, share the extensive expansion and sequence diversification of the TS gene family. Altogether, our results are congruent with the evolutionary history of the T. cruzi clade and represent a contribution to the understanding of the molecular evolution and role of TS proteins in trypanosomes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts., Methodology/principal Findings: The T. rangeli haploid genome is ∼ 24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heat-shock proteins., Conclusions/significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets.

We assessed the biological value of an okara diet and its effects on the hormonal and metabolic profile of rats submitted to protein restriction during intra-uterine life and lactation and recovered after weaning. Male rats from mothers fed either 17% or 6% protein during pregnancy and lactation were maintained on 17% casein (CC, LC), 17% okara (CO, LO) or 6% casein (LL) diets over 60 d. The nutritional quality of the okara protein was similar to that of casein. The okara diet was effective in the nutritional recovery of rats in growing that were malnourished in early life. Furthermore, the okara diet reversed the hypercholesterolemia and the hepatic steatosis observed in the malnutrition and prevented glucose intolerance in an animal model prone to diabetes mellitus.

Chagas disease is caused by the protozoan Trypanosoma cruzi which affects 10 million people worldwide. Very few kinases have been characterized in this parasite, including the phosphatidylinositol kinases (PIKs) that are at the heart of one of the major pathways of intracellular signal transduction. Recently, we have classified the PIK family in T. cruzi using five different models based on the presence of PIK conserved domains. In this study, we have mapped PIK genes to the chromosomes of two different T. cruzi lineages (G and CL Brener) and determined the cellular localization of two PIK members. The kinases have crucial roles in metabolism and are assumed to be conserved throughout evolution. For this reason, they should display a conserved localization within the same eukaryotic species. In spite of this, there is an extensive polymorphism regarding PIK localization at both genomic and cellular levels, among different T. cruzi isolates and between T. cruzi and Trypanosomabrucei, respectively. We showed in this study that the cellular localization of two PIK-related proteins (TOR1 and 2) in the T. cruzi lineage is distinct from that previously observed in T. brucei. In addition, we identified a new PIK gene with peculiar feature, that is, it codes for a FYVE domain at N-terminal position. FYVE-PIK genes are phylogenetically distant from the groups containing exclusively the FYVE or PIK domain. The FYVE-PIK architecture is only present in trypanosomatids and in virus such as Acanthamoeba mimivirus, suggesting a horizontal acquisition. Our Bayesian phylogenetic inference supports this hypothesis. The exact functions of this FYVE-PIK gene are unknown, but the presence of FYVE domain suggests a role in membranous compartments, such as endosome. Taken together, the data presented here strengthen the possibility that trypanosomatids are characterized by extensive genomic plasticity that may be considered in designing drugs and vaccines for prevention of Chagas disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: As population ageing becomes a global phenomenon the need to understand the quality of life of older people around the world has become increasingly salient. The CASP-19 is a well established measure of quality of later life. The scale is composed of 19 items which map onto the four domains of control (C), Autonomy (A), Self-Realisation (S) and Pleasure (P). It has already been translated to 12 languages and has been used in a number of national and international studies. However use of the scale outside of Europe has been very limited. The objective of this study was to translate and evaluate the use of the CASP-19 amongst older Brazilians., Methods: The CASP-19 was translated from English to Portuguese, back-translated and submitted to an analysis of equivalence by a committee of judges. The scale was then administered to a sample of community dwelling older people in Recife, Brazil (n = 87), and tested for psychometric properties. The Control and Pleasure domains exhibited good internal consistency. By removing one item from each of the Autonomy and Self Realisation domains their internal consistency was improved., Results: The mean age of the sample was 75.6±0.7 years, subjects were mainly female (52.9%), white (52.9%), who lived without a partner (54%), and had a monthly income varying from USD 340.00 to USD 850.00. Translation and cross-cultural adaptation permitted good understanding and applicability of final version. Psychometric analyses revealed that the removal of two items improved the internal consistency of the Autonomy and Pleasure domains. Confirmatory factor analyses suggest that a 16 item, four factor, model best fits the data., Conclusion: In this small exploratory study the CASP-19 Brazil demonstrated good psychometric properties. It was easy to use for both participants and researchers. Hopefully future studies in Brazil will employ the scale so that more direct cross national comparisons can be made with older people in Europe and the US.

Background: One of the chief complaints of individuals who frequent the Family Health Units is chronic pain which, in Salvador, affects over 40% of the population. However, little is known about the type of pain and its impact on quality of life (QoL) at population level. The aim of the study is to evaluate the impact of neuropathic pain on QoL in a community., Methods: A descriptive cross-sectional study was conducted from March to October 2012, in a Family Health Unit, Salvador, Bahia, Brazil. The DN-4 (type of pain), body map (location), VAS (intensity) and SF-36 (QoL) instruments were applied. The Chi-square (univariate analysis) and logistic regression (multivariate) tests were used, with IC 95% and P < 0.05., Results: In a sample of 191 individuals with chronic pain, predominantly women (86.4%), single (48.7%), nonwhite (93.2%), low educational (46.6%) and low economic (100%) level. The most affected locations of the body were knees, lumbar region and head. In 60.2% of interviewees, neuropathic pain, of high intensity (VAS = 7.09 ± 3.0) predominated, with duration of 8.53 ± 8.8 years and mean QoL was reduced in 47.13%., Conclusions: Intense pain in the dorsal region and type of neuropathy are independent predictors for greater compromise of QoL.

Introduction: Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). Herein we evaluate the dose-response effect of low-level laser therapy (LLLT) on lung inflammation induced by i-I/R., Methods: Mice were subjected to mesenteric artery occlusion (45 min) and killed after clamp release and intestinal reperfusion (2h). Increasing doses (1, 3, 5 and 7,5 J/cm(2)) of laser irradiation (660 nm) was carried out on the mice skin over the upper bronchus for 5 min after initiating reperfusion. Neutrophils activation was determined by myeloperoxidase (MPO) activity. The mRNA expression and protein concentration of inflammatory mediators IL-1β, IL-6, TNF and IL-10 in lung were measured by RT-PCR and ELISA, respectively., Results: With exception of 1J/cm(2), LLLT reduced MPO activity as well as IL-1β levels in the lungs from inflamed mice. LLLT was also markedly effective in reducing both IL-6 and TNF expression and levels in the lungs from mice submitted to i-I/R in all laser doses studied. Otherwise, LLLT significantly increased the protein levels of IL-10 in inflamed mice by i-I/R; however only in the dose of 1J/cm(2)., Conclusion: We conclude that the LLLT is able to control the neutrophils activation and proinflammatorycytokines release into the lungs in a model of i-I/R in mice.

A growing body of evidence in mammalian cells indicates that secreted vesicles can be used to mediate intercellular communication processes by transferring various bioactive molecules, including mRNAs and microRNAs. Based on these findings, we decided to analyze whether Trypanosoma cruzi-derived extracellular vesicles contain RNA molecules and performed a deep sequencing and genome-wide analysis of a size-fractioned cDNA library (16-40nt) from extracellular vesicles secreted by noninfective epimastigote and infective metacyclic trypomastigote forms. Our data show that the small RNAs contained in these extracellular vesicles originate from multiple sources, including tRNAs. In addition, our results reveal that the variety and expression of small RNAs are different between parasite stages, suggesting diverse functions. Taken together, these observations call attention to the potential regulatory functions that these RNAs might play once transferred between parasites and/or to mammalian host cells., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Sporotrichosis is a polymorphic disease caused by a complex of thermodimorphic fungi including S. brasiliensis, S. schenckii sensu stricto (s. str.), S. globosa and S. luriei. Humans and animals can acquire the disease through traumatic inoculation of propagules into the subcutaneous tissue. Despite the importance of sporotrichosis as a disease that can take epidemic proportions there are just a few studies dealing with genetic polymorphisms and genomic architecture of these pathogens. The main objective of this study was to investigate chromosomal polymorphisms and genomic organization among different isolates in the S. schenckii complex. We used pulsed field gel electrophoresis (PFGE) to separate chromosomal fragments of isolated DNA, followed by probe hybridization. Nine loci (β-tubulin, calmodulin, catalase, chitin synthase 1, Internal Transcribed Spacer, Pho85 cyclin-dependent kinase, protein kinase C Ss-2, G protein α subunit and topoisomerase II) were mapped onto chromosomal bands of Brazilian isolates of S. schenckii s. str. and S. brasiliensis. Our results revealed the presence of intra and interspecies polymorphisms in chromosome number and size. The gene hybridization analysis showed that closely related species in phylogenetic analysis had similar genetic organizations, mostly due to identification of synteny groups in chromosomal bands of similar sizes. Our results bring new insights into the genetic diversity and genome organization among pathogenic species in the Sporothrix schenckii complex.

Trypanosoma cruzi comprises a pool of populations which are genetically diverse in terms of DNA content, growth and infectivity. Inter- and intra-strain karyotype heterogeneities have been reported, suggesting that chromosomal rearrangements occurred during the evolution of this parasite. Clone D11 is a single-cell-derived clone of the T. cruzi G strain selected by the minimal dilution method and by infecting Vero cells with metacyclic trypomastigotes. Here we report that the karyotype of clone D11 differs from that of the G strain in both number and size of chromosomal bands. Large chromosomal rearrangement was observed in the chromosomes carrying the tubulin loci. However, most of the chromosome length polymorphisms were of small amplitude, and the absence of one band in clone D11 in relation to its reference position in the G strain could be correlated to the presence of a novel band migrating above or below this position. Despite the presence of chromosomal polymorphism, large syntenic groups were conserved between the isolates. The appearance of new chromosomal bands in clone D11 could be explained by chromosome fusion followed by a chromosome break or interchromosomal exchange of large DNA segments. Our results also suggest that telomeric regions are involved in this process. The variant represented by clone D11 could have been induced by the stress of the cloning procedure or could, as has been suggested for Leishmania infantum, have emerged from a multiclonal, mosaic parasite population submitted to frequent DNA amplification/deletion events, leading to a 'mosaic' structure with different individuals having differently sized versions of the same chromosomes. If this is the case, the variant represented by clone D11 would be better adapted to survive the stress induced by cloning, which includes intracellular development in the mammalian cell. Karyotype polymorphism could be part of the T. cruzi arsenal for responding to environmental pressure.

Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). It is not known if pro- and anti-inflammatory mediators in ARDS induced by i-I/R can be controlled by low-level laser therapy (LLLT). This study was designed to evaluate the effect of LLLT on tracheal cholinergic reactivity dysfunction and the release of inflammatory mediators from the lung after i-I/R. Anesthetized rats were subjected to superior mesenteric artery occlusion (45 min) and killed after clamp release and preestablished periods of intestinal reperfusion (30 min, 2 or 4 h). The LLLT (660 nm, 7.5 J/cm(2)) was carried out by irradiating the rats on the skin over the right upper bronchus for 15 and 30 min after initiating reperfusion and then euthanizing them 30 min, 2, or 4 h later. Lung edema was measured by the Evans blue extravasation technique, and pulmonary neutrophils were determined by myeloperoxidase (MPO) activity. Pulmonary tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1), and isoform of NO synthase (iNOS) mRNA expression were analyzed by real-time PCR. TNF-α, IL-10, and iNOS proteins in the lung were measured by the enzyme-linked immunoassay technique. LLLT (660 nm, 7.5 J/cm(2)) restored the tracheal hyperresponsiveness and hyporesponsiveness in all the periods after intestinal reperfusion. Although LLLT reduced edema and MPO activity, it did not do so in all the postreperfusion periods. It was also observed with the ICAM-1 expression. In addition to reducing both TNF-α and iNOS, LLLT increased IL-10 in the lungs of animals subjected to i-I/R. The results indicate that LLLT can control the lung's inflammatory response and the airway reactivity dysfunction by simultaneously reducing both TNF-α and iNOS.

It remains unknown if the oxidative stress can be regulated by low-level laser therapy (LLLT) in lung inflammation induced by intestinal reperfusion (i-I/R). A study was developed in which rats were irradiated (660 nm, 30 mW, 5.4 J) on the skin over the bronchus and euthanized 2 h after the initial of intestinal reperfusion. Lung edema and bronchoalveolar lavage fluid neutrophils were measured by the Evans blue extravasation and myeloperoxidase (MPO) activity respectively. Lung histology was used for analyzing the injury score. Reactive oxygen species (ROS) was measured by fluorescence. Both expression intercellular adhesion molecule 1 (ICAM-1) and peroxisome proliferator-activated receptor-y (PPARy) were measured by RT-PCR. The lung immunohistochemical localization of ICAM-1 was visualized as a brown stain. Both lung HSP70 and glutathione protein were evaluated by ELISA. LLLT reduced neatly the edema, neutrophils influx, MPO activity and ICAM-1 mRNA expression. LLLT also reduced the ROS formation and oppositely increased GSH concentration in lung from i-I/R groups. Both HSP70 and PPARy expression also were elevated after laser irradiation. Results indicate that laser effect in attenuating the acute lung inflammation is driven to restore the balance between the pro- and antioxidants mediators rising of PPARy expression and consequently the HSP70 production., (© 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.)

The effects of LED therapy at 940 nm on periodontal healing, inflammatory cell infiltration, and root resorption were analyzed in an experimental model of orthodontic tooth movement in rats. Twenty-five male Wistar rats were allocated into four experimental groups: Control animals (Co, n = 5), Controls + LED therapy (CoLED, n = 6), animals submitted to orthodontic force (RR, n = 7) and submitted to orthodontic force + LED therapy (RRLED, n = 7). All procedures were approved by the Committee for Ethics in Animal Experimentation of the Universidade Estadual de Londrina (protocol CEEA 5/2010 37359). A force of 50 g was applied to the right upper molars of RR and RRLED groups. On days 2, 3, and 4 after orthodontic treatment, the CoLED and RRLED groups received LED irradiation (940 nm, 4 J/cm(2)). The animals were killed on day 7 for histological analysis. An increased number of root resorption lacunae was found only in the RR group (p < 0.05). The RR group also presented more osteoclasts (p < 0.005) and inflammatory cell infiltration (p < 0.005) than the control group. The RRLED group presented fewer osteoclasts (p < 0.005) and inflammatory cells (p < 0.005) in the periodontal ligament than the RR group. The CoLED and RRLED groups presented more periodontal fibroblasts (p < 0.005) than non-irradiated groups. RRLED presented more blood vessels (p < 0.01) in the periodontal ligament than the RR group. In conclusion, the results suggest that LED therapy improved periodontal tissue repair and decreased inflammation and root resorption after the application of orthodontic force.

The aim of this work is to analyze the effects of LED therapy at 940 nm or cold water immersion therapy (CWI) after an acute bout of exercise on markers of muscle damage and inflammation. Thirty-two male Wistar rats were allocated into four groups: animals kept at rest (control), exercised animals (E), exercised + CWI (CWI), and exercised + LED therapy (LED). The animals swam for 100 min, after which blood samples were collected for lactate analysis. Animals in the E group were returned to their cages without treatment, the CWI group was placed in cold water (10°C) for 10 min and the LED group received LED irradiation on both gastrocnemius muscles (4 J/cm(2) each). After 24 h, the animals were killed and the soleus muscles were submitted to histological analysis. Blood samples were used for hematological and CK analyses. The results demonstrated that the LED group presented fewer areas of muscle damage and inflammatory cell infiltration and lower levels of CK activity than the E group. Fewer areas of damaged muscle fiber were observed in the LED group than in CWI. CWI and LED did not reduce edema areas. Hematological analysis showed no significant effect of either treatment on leukocyte counts. The results suggest that LED therapy is more efficient than CWI in preventing muscle damage and local inflammation after exercise.

Background: The subtelomeres of many protozoa are highly enriched in genes with roles in niche adaptation. T. cruzi trypomastigotes express surface proteins from Trans-Sialidase (TS) and Dispersed Gene Family-1 (DGF-1) superfamilies which are implicated in host cell invasion. Single populations of T. cruzi may express different antigenic forms of TSs. Analysis of TS genes located at the telomeres suggests that chromosome ends could have been the sites where new TS variants were generated. The aim of this study is to characterize telomeric and subtelomeric regions of T. cruzi available in TriTrypDB and connect the sequences of telomeres to T. cruzi working draft sequence., Results: We first identified contigs carrying the telomeric repeat (TTAGGG). Of 49 contigs identified, 45 have telomeric repeats at one end, whereas in four contigs the repeats are located internally. All contigs display a conserved telomeric junction sequence adjacent to the hexamer repeats which represents a signature of T. cruzi chromosome ends. We found that 40 telomeric contigs are located on T. cruzi chromosome-sized scaffolds. In addition, we were able to map several telomeric ends to the chromosomal bands separated by pulsed-field gel electrophoresis.The subtelomeric sequence structure varies widely, mainly as a result of large differences in the relative abundance and organization of genes encoding surface proteins (TS and DGF-1), retrotransposon hot spot genes (RHS), retrotransposon elements, RNA-helicase and N-acetyltransferase genes. While the subtelomeric regions are enriched in pseudogenes, they also contain complete gene sequences matching both known and unknown expressed genes, indicating that these regions do not consist of nonfunctional DNA but are instead functional parts of the expressed genome. The size of the subtelomeric regions varies from 5 to 182 kb; the smaller of these regions could have been generated by a recent chromosome breakage and telomere healing event., Conclusions: The lack of synteny in the subtelomeric regions suggests that genes located in these regions are subject to recombination, which increases their variability, even among homologous chromosomes. The presence of typical subtelomeric genes can increase the chance of homologous recombination mechanisms or microhomology-mediated end joining, which may use these regions for the pairing and recombination of free ends.