Multiplexed cellular profiling identifies an organoselenium compound as an inhibitor of CRM1-mediated nuclear export.

Chromosomal region maintenance 1 (CRM1 also known as Xpo1 and exportin-1) is the receptor for the nuclear export controlling the intracellular localization and function of many cellular and viral proteins that play a crucial role in viral infections and cancer. The inhibition of CRM1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses, for the treatment of cancer, and to overcome therapy resistance. Recently, selinexor has been approved as the first CRM1 inhibitor for the treatment of multiple myeloma, providing proof of concept for this therapeutic option with a new mode of action. However, selinexor is associated with dose-limiting toxicity and hence, the discovery of alternative small molecule leads that could be developed as less toxic anticancer and antiviral therapeutics will have a significant impact in the clinic. Here, we report a CRM1 inhibitor discovery platform. The development of this platform includes reporter cell lines that monitor CRM1 activity by using red fluorescent protein or green fluorescent protein-labeled HIV-1 Rev protein with a strong heterologous nuclear export signal. Simultaneously, the intracellular localization of other proteins, to be interrogated for their capacity to undergo CRM1-mediated export, can be followed by co-culturing stable cell lines expressing fluorescent fusion proteins. We used this platform to interrogate the mode of nuclear export of several proteins, including PDK1, p110α, STAT5A, FOXO1, 3, 4 and TRIB2, and to screen a compound collection. We show that while p110α partially relies on CRM1-dependent nuclear export, TRIB2 is exported from the nucleus in a CRM1-independent manner. Compound screening revealed the striking activity of an organoselenium compound on the CRM1 nuclear export receptor.

mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity.

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment. One major regulatory input of FOXO signaling is mediated by protein kinases. Here, we use specific inhibitors against different kinases including PI3K, mTOR, MEK and ALK, and other receptor tyrosine kinases (RTKs) to determine their effect on FOXO3 activity. While we show that inhibition of PI3K efficiently drives FOXO3 into the cell nucleus, the dual PI3K/mTOR inhibitors dactolisib and PI-103 induce nuclear FOXO translocation more potently than the PI3Kδ inhibitor idelalisib. Furthermore, specific inhibition of mTOR kinase activity affecting both mTORC1 and mTORC2 potently induced nuclear translocation of FOXO3, while rapamycin, which specifically inhibits the mTORC1, failed to affect FOXO3. Interestingly, inhibition of the MAPK pathway had no effect on the localization of FOXO3 and upstream RTK inhibition only weakly induced nuclear FOXO3. We also measured the effect of the test compounds on the phosphorylation status of AKT, FOXO3 and ERK, on FOXO-dependent transcriptional activity and on the subcellular localization of other FOXO isoforms. We conclude that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.

Pelvic floor muscle training adapted for urinary incontinence in multiple sclerosis: a randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: Lower urinary tract symptoms (LUTS) affect up to 80% of patients with multiple sclerosis (MS). The present randomized, open-label, clinical trial examines the effectiveness, as a conservative treatment for LUTS, of a physiotherapist-guided pelvic floor muscle training (PFMT) program adapted for patients with relapsing-remitting multiple sclerosis (RRMS) and urinary incontinence (UI). METHODS: Forty-eight patients with RRMS were randomly assigned to a 12-week PFMT program with or without physiotherapist guidance. The primary endpoint was the reduction in urinary leakages after 12 weeks of following the program. The secondary variables assessed were quality of life (QoL), UI severity, LUTS, and treatment adherence. RESULTS: Forty patients completed the program. No significant differences in baseline characteristics were seen between the two treatment groups. At 12 weeks, both groups reported a significantly reduced number of leakages compared with baseline (P < 0.001), with no significant differences seen between groups (P = 0.210). In the physiotherapist-guided group, significant differences were found in QoL, UI severity, and LUTS between baseline and 12 weeks, for both male and female subjects. No significant differences in adherence were seen between the two treatment groups. CONCLUSIONS: No difference in leakage reduction was seen between physiotherapist-guided and unguided PFMT. However, the physiotherapist-guided program was associated with improvements in UI severity, QoL, and LUTS in women and men. The guided PFMT group also showed a trend towards better adherence to treatment. CLINICAL TRIAL REGISTRATION: No. NCT03000647; Title: "Guided Versus Non-Guided Pelvic Floor Exercises for Urinary Incontinence in Relapsing-Remitting Multiple Sclerosis."

High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.

The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or "gutless". Compared with earlier generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remarkable efficacy of in vivo transduction, and production at high titers. More importantly, the lack of viral coding sequences in the genomes of HC-AdVs extends the cloning capacity up to 37 Kb, and allows long-term episomal persistence of transgenes in non-dividing cells. These properties open a wide repertoire of therapeutic opportunities in the fields of gene supplementation and gene correction, which have been explored at the preclinical level over the past two decades. During this time, production methods have been optimized to obtain the yield, purity, and reliability required for clinical implementation. Better understanding of inflammatory responses and the implementation of methods to control them have increased the safety of these vectors. We will review the most significant achievements that are turning an interesting research tool into a sound vector platform, which could contribute to overcome current limitations in the gene therapy field.

Scene-Based Psychodramatic Family Therapy With Troubled Adolescents and Parents: A Pilot Study.

Scene-Based Psychodramatic Family Therapy (SB-PFT) is an innovative treatment used with troubled adolescents and their parents to improve family relationships and reduce adolescents' problematic behavior. It integrates the principles of family therapy, psychodrama, and multiple-family group methodology. This research is a pilot study to obtain empirical evidence on the SB-PFT therapeutic process by gauging the perception of change of troubled adolescents and their parents, and assess the perceived helpfulness of its methodology and techniques. Ten multiple-family intervention groups were drawn up, with 110 participants (63 adolescents and 47 parents), and we adopted a qualitative methodology with focus groups, using an inductive analysis of 290 active constructions of participant narratives. Concerning perception of change, the adolescents reported mainly gaining in social support, prosocial attitudes, keys to problem solving, and expression of emotions due to the treatment. The parents perceived improvement in social support, keys for educational practices, emotional well-being, and expression of emotions due to the treatment. Regarding the perceived helpfulness of methodology and techniques, both adolescents and parents highlighted the usefulness of the group methodology for gaining social support, relativizing the problem, and expressing emotions. Additionally, participants referred to role-playing and mirror techniques as the most useful techniques. In conclusion, this first study on SB-PFT presents and describes its treatment for troubled adolescents and their parents. The participants' positive perception of their personal and relational change after treatment should serve to promote further studies with quantitative methodology in order to verify the effectiveness of SB-PFT treatment.

La terapia familiar psicodramática basada en escenas (SB-PFT, por sus siglas en inglés) es un tratamiento innovador usado con adolescentes conflictivos y sus padres para mejorar las relaciones familiares y disminuir el comportamiento problemático de los adolescentes. Integra los principios de la terapia familiar, del psicodrama y de la metodología grupal multifamiliar. Esta investigación es un estudio piloto para obtener conocimiento empírico sobre el proceso terapéutico de la SB-PFT mediante la medición de la percepción de cambio de los adolescentes conflictivos y sus padres, y para evaluar la utilidad percibida de esta metodología y técnica. Se formaron diez grupos multifamiliares de intervención con 110 participantes (63 adolescentes y 47 padres), y adoptamos una metodología cualitativa con grupos focales utilizando un análisis inductivo de 290 construcciones activas de historias de los participantes. Con respecto a la percepción de cambio, los adolescentes informaron un aumento pricipalmente del apoyo social, de las actitudes prosociales, de las claves para resolver problemas y de la expresión de emociones debido al tratamiento. Los padres percibieron una mejora del apoyo social, de las claves para las prácticas educativas, del bienestar emocional y de la expresión de emociones debido al tratamiento. Con respecto a la utilidad percibida de la metodología y las técnicas, tanto los adolescentes como los padres destacaron la utilidad de la metodología de grupo para obtener apoyo social, relativizar el problema y expresar emociones. Además, los participantes se refirieron al juego de roles y a las técnicas del espejo como las más útiles. En resumen, este primer estudio sobre la SB-PFT presenta y describe su tratamiento para adolescentes conflictivos y sus padres. La percepción positiva de los participantes de su cambio personal y relacional después del tratamiento debería servir para promover más estudios con una metodología cuantitativa a fin de verificar la eficacia del tratamiento con la SB-PFT.

Hydrolysed Collagen from Sheepskins as a Source of Functional Peptides with Antioxidant Activity.

The extraction and enzymatic hydrolysis of collagen from sheepskins at different times of hydrolysis (0, 10, 15, 20, 30 min, 1, 2, 3 and 4 h) were investigated in terms of amino acid content (hydroxyproline), isoelectric point, molecular weight (Mw) by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method, viscosity, Fourier-transform infrared (FTIR) spectroscopy, antioxidant capacity by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, thermal properties (Differential Scanning Calorimetry) and morphology by scanning electron microscopy (SEM) technique. The kinetics of hydrolysis showed an increase in the protein and hydroxyproline concentration as the hydrolysis time increased to 4 h. FTIR spectra allowed us to identify the functional groups of hydrolysed collagen (HC) in the amide I region for collagen. The isoelectric point shifted to lower values compared to the native collagen precursor. The change in molecular weight and viscosity from time 0 min to 4 h promoted important antioxidant activity in the resulting HC. The lower the Mw, the greater the ability to donate an electron or hydrogen to stabilize radicals. From the SEM images it was evident that HC after 2 h had a porous and spongy structure. These results suggest that HC could be a good alternative to replace HC from typical sources like pigs, cows and fish.

Perceived Impact, Needs, and Resources of Grandparents of Children and Adolescents on the Autism Spectrum: A Qualitative Study.

Grandparents play different roles in families of children and adolescents on the autism spectrum. They are frequently engaged in caregiving tasks with the person on the autism spectrum, providing emotional and instrumental support to the family. However, despite their frequent involvement and the importance of their role in the family, there are few studies that address the experiences of these grandparents, particularly in the Spanish and southern Europe context. This study explores the impact and needs of having a grandchild on the autism spectrum and the resources that grandparents have and use to face the difficulties that arise. A semi-structured interview was carried out with 17 grandparents of children and adolescents on the autism spectrum. We conducted a coding reliability thematic analysis of the impact and used a quantitative content analysis of grandparents' needs and resources. Results indicated three main aspects related to the impact: personal growth, wanting to help and not being able to, and suffering at three levels: for themselves, their sons and daughters, and grandchildren. Grandparents perceived needs in four contexts: their own needs, the needs of the nuclear family, the needs of the person on the autism spectrum, and the needs of society. The most frequent needs were informational and management of behavioral difficulties. In the resources, the most frequently used strategies were religious beliefs and informal support seeking. It is essential to address the quality of parents-grandparents' relationships, and include grandparents in intervention programmes, as a way of addressing grandparents' needs.

Teaching protein structure and function through molecular visualization.

The function of proteins is governed by their three-dimensional structure. This structure is determined by the chemical characteristics and atomic interactions of amino acids. Students of biochemistry, with a particular focus on protein chemistry, benefit from looking at protein structures and understanding how proteins are built and fold. Due to their three-dimensional nature, static two-dimensional representations in textbooks can be limiting to student learning. Here, we developed a series of tutorials that introduce students to molecular graphics software. The students are challenged to apply the software to look at proteins and to get a deeper understanding of how amino acid properties are linked to structure. We also familiarize students with some of the latest tools in computational structural biology. Students performed the tutorials with visual enthusiasm and reported general satisfaction in being able to visualize theoretical concepts learned during lectures. We further stimulated student engagement by allowing space for self-exploration. We share the tutorial instructions for other teachers to build on them, and we also offer suggestions for further improvement based on student feedback. In summary, we present a series of tutorials aimed at students of an advanced course in protein biochemistry to enable them to explore the universe of protein structures and how those relate to function.

Parental Attachment and Psychosocial Adjustment in Adolescents Exposed to Marital Conflict.

(1) Background: Interparental conflict is a phenomenon that poses a serious threat not only to the quality of life of the couple but also to the father-child relationship, mother-child relationship, and well-being of adolescents. This study examined the difference in parental attachment and adjustment in adolescents exposed to marital conflict versus those not exposed to parental conflicts in low-income areas. (2) Methods: 67 adolescents involved in Child Welfare Services (CWS) in disadvantaged neighbourhoods in southern Spain were examined. The sample was split into two groups according to the exposure to marital conflict. Subsequently, differences between groups were analysed on father attachment, mother attachment, aggression, antisocial behaviour, and emotional intelligence. (3) Results: Primarily, the data showed significantly worse attachment with the father among conflict-exposed versus non-conflict-exposed adolescents. These results were not found for the attachment with the mother. Additionally, greater anger and worse stress management were found in conflict-exposed adolescents. (4) Conclusions: The results partially confirmed the spillover and compensatory hypothesis. Practical implications point out that developing preventive interventions that protect the father-adolescent attachment in situations of family conflict is recommended.

Taenia solium TAF6 and TAF9 bind to a downstream promoter element present in the Tstbp1 gene core promoter.

Transcription regulation in cestodes has been little studied. Here, we characterize the Taenia solium TATA-binding protein (TBP) gene. We found binding sites for transcription factors such as NF1, YY1, and AP-1 in the proximal promoter. We also identified two TATA-like elements in the promoter; however, neither could bind TBP. Additionally, we mapped the transcription start site (A+1) within an initiator and identified a putative downstream promoter element (DPE) located at +27 bp relative to the transcription start site. These two elements are important and functional for gene expression. Moreover, we identified the genes encoding T. solium TBP-Associated Factor 6 (TsTAF6) and 9 (TsTAF9). A Western blot assay revealed that both factors are expressed in the parasite; electrophoretic mobility shift assays and super-shift assays revealed interactions between the DPE probe and TsTAF6-TsTAF9. Finally, we used molecular dynamics simulations to formulate an interaction model among TsTAF6, TsTAF9, and the DPE probe; we stabilized the model with interactions between the histone fold domain pair in TAFs and several pairs of nucleotides in the DPE probe. We discuss novel and interesting features of the TsTAF6-TsTAF9 complex for interaction with DPE on T. solium promoters.

Biochemical characterization and gene structure analysis of the 24-kDa glutathione transferase sigma from Taenia solium.

Taenia solium can cause human taeniasis and/or cysticercosis. The latter can in some instances cause human neurocysticercosis which is considered a priority in disease-control strategies and the prevention of mental health problems. Glutathione transferases are crucial for the establishment and long-term survival of T. solium; therefore, we structurally analyzed the 24-kDa glutathione transferase gene (Ts24gst) of T. solium and biochemically characterized its product. The gene promoter showed potential binding sites for transcription factors and xenobiotic regulatory elements. The gene consists of a transcription start site, four exons split by three introns, and a polyadenylation site. The gene architecture is conserved in cestodes. Recombinant Ts24GST (rTs24GST) was active and dimeric. Anti-rTs24GST serum showed slight cross-reactivity with human sigma-class GST. A 3D model of Ts24GST enabled identification of putative residues involved in interactions of the G-site with GSH and of the H-site with CDNB and prostaglandin D2. Furthermore, rTs24GST showed optimal activity at 45 °C and pH 9, as well as high structural stability in a wide range of temperatures and pHs. These results contribute to the better understanding of this parasite and the efforts directed to fight taeniasis/cysticercosis.

Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study.

Background: ATTR-CM is becoming more prevalent, and disease-modifying therapy has been investigated in recent years with promising results. Diflunisal has shown TTR-stabilizing properties assessed by biomarkers and echocardiography, but there are no trials addressing the evolution of morphological changes with CMR. Methods and Results: AMILCA-DIFLU is an exploratory pilot study prospective, single-center, non-randomized, open-label clinical trial. Patients diagnosed with ATTR-CM underwent clinical, functional, biochemical and imaging assessment before and one year after diflunisal therapy initiation. Of the twelve ATTR-CM patients included, only nine patients completed treatment and study protocol in 12 months. To increase the sample size, we included seven real-world patients with one year of diflunisal treatment. Among the group of patients who completed treatment, diflunisal therapy did not show improvement in cardiac disease status as assessed by many cardiac and inflammatory biomarkers, 6MWT and CMR parameters after one year of treatment. However, a non-significant trend towards stabilization of CMR parameters such as LVEF, ECV and T2 at one year was found. When comparing the group of patients who completed diflunisal therapy and those who did not, a significant decrease in the distance performed in the 6MWT was found in the group of patients who completed treatment at one year (-14 ± 81.8 vs. -173 ± 122.2; p = 0.032). Diflunisal was overall well tolerated, showing only a statistically significant worsening in renal function in the group of diflunisal-treatment patients with no clinical relevance or need for treatment discontinuation. Conclusions: In patients with ATTR-CM, treatment with diflunisal was overall well tolerated and tended to stabilize or slow down amyloid cardiac disease progression assessed by CMR parameters, cardiac and inflammatory biomarkers and functional capacity.

Cyclosporin A as an Add-On Therapy to a Corticosteroid-Based Background Treatment in Patients with COVID-19: A Multicenter, Randomized Clinical Trial.

Background: In susceptible hosts, SARS-CoV2-induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as an add-on therapy to the standard of care (SoC) in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to eight Spanish tertiary hospitals. Patients were stratified into two severity categories and randomized in a 1:1 ratio to receive a corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by Day 12 without relapses. Results: 109 patients were included and randomized, and 98 of them considered for the mITT population (51 assigned to the CsA + SoC group and 47 to the SoC group). A total of 35 (68.6%) patients from the CsA + SoC group and 32 (71.1%) patients from the SoC group reached the primary endpoint in the mITT analysis. No differences were found after stratification into age groups, in the severity level at admission, or in a combination of both. Overall, the time to FiO2 normalization was 7.4 days vs. 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: The addition of CsA did not show differences over a corticosteroid-based treatment in the clinical course of the included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies.

Serum Biomarkers and Their Association with Myocardial Function and Exercise Capacity in Cardiac Transthyretin Amyloidosis.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR amyloidosis) is a frequent etiology of heart failure. Inflammation and mineral metabolism are associated with myocardial dysfunction and clinical performance. Cardiac global longitudinal strain (GLS) allows function assessment and is associated with prognosis. Our aim was to describe possible correlations between GLS, biomarker levels and clinical performance in ATTR amyloidosis. METHODS: Thirteen patients with ATTR amyloidosis were included. Clinical characteristics; echocardiographic features, including strain assessment and 6 min walk test (6MWT); and baseline inflammatory, mineral metabolism and cardiovascular biomarker levels were assessed. RESULTS: Of the 13 patients, 46.2% were women, and the mean age was 79 years. TAPSE correlated with NT-ProBNP (r -0.65, p < 0.05) and galectin-3 (r 0.76, p < 0.05); E/E' ratio correlated with hsCRP (r 0.58, p < 0.05). Left ventricular GLS was associated with NT-ProBNP (r 0.61, p < 0.05) (patients have a better prognosis if the strain value is more negative) and left atrial GLS with NT-ProBNP (r -0.73, p < 0.05) and MCP1 (r 0.55, p < 0.05). Right ventricular GLS was correlated with hsTnI (r 0.62, p < 0.05) and IL6 (r 0.881, p < 0.05). Klotho levels were correlated with 6MWT (r 0.57, p < 0.05). CONCLUSIONS: While inflammatory biomarkers were correlated with cardiac function, klotho levels were associated with clinical performance in the population with TTR-CA.

Romani Girls Matter: Developing a Participatory Action Research Protocol for Reproductive Justice.

Despite the last few decades' advances towards social and gender justice, reproductive decisions are still a source of oppression for many European Romani women and girls. This protocol aims to propose a model to empower Romani women and girls' reproductive decisions, inspired by Reproductive Justice-the recognition of women and girls' ability to make safe and free decisions about their bodies and reproduction. Through Participatory Action Research, 15-20 Romani girls and their families, two Romani platforms, and key agents from a rural and an urban context in Spain will participate. They will (1) contextualize Romani women and girls' inequities, (2) build partnerships, (3) implement Photovoice and advocate for their gender rights, and (4) assess the initiative's related changes, using self-evaluation techniques. Qualitative and quantitative indicators will be collected to assess impacts among participants, while tailoring and assuring the quality of the actions. Expected outcomes include the creation and consolidation of new social networks, and the promotion of Romani women and girls' leadership. For this, Romani organizations must be transformed into empowering settings for their communities, spaces where Romani women and girls assume responsibility of the initiatives, being these tailored to their real needs and interests, and guaranteeing transformative social changes.

Examining the Relationship between Dietary Intake, Socioeconomic Status, and Systolic Blood Pressure of Adults on Hemodialysis in Quito, Ecuador.

Background: In Ecuador, the number of adults on hemodialysis (HD) continues to rise. Currently, the effect dietary habits and socioeconomic status (SES) have on blood pressure is not known for those on HD. Objectives: The objectives of this study focused on adults on HD in Quito, Ecuador to 1) assess the relationship between dietary intake and SES; 2) compare dietary intake to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines; and 3) explore the relationship between dietary intake and systolic blood pressure. Methods: This cross-sectional study was conducted at the dialysis center within Eugenio Espejo Specialties Hospital in Quito, Ecuador between May and June 2022 among 50 adults on HD. Three 24-h recalls were used to determine average dietary intake and the 25-item Instituto Nacional de Estadística y Censos-Stratification of SES was used to determine SES. Electrolytes and 2 blood pressure readings were collected. Qualitative narrative data analysis was performed to identify themes using NVivo v12. T-tests of independence, simple, and multiple linear regressions using age and sex as confounders were conducted using R and a P < 0.05 was deemed as statistically significant. Results: On an average, 76% of participants consumed <25 kcal/kg body weight energy and 64% consumed <1 g protein/kg body weight. Participants consumed less energy and protein compared with the KDOQI guidelines (P < 0.05). Positive relationships were observed with potassium and blood pressure (ß = 0.020, P < 0.05) and SES with energy, protein, and phosphorus (P < 0.05). Themes that were identified as contributing to dietary intake were limited knowledge, lack of consistency with dietary information, and limited appetite. Conclusions: Findings from this study indicate that the focus should be on improving energy and protein intake for this population.

Differential Protein Expression of Taenia crassiceps ORF Strain in the Murine Cysticercosis Model Using Resistant (C57BL/6) Mice.

A cysticercosis model of Taenia crassiceps ORF strain in susceptible BALB/c mice revealed a Th2 response after 4 weeks, allowing for the growth of the parasite, whereas resistant C57BL/6 mice developed a sustained Th1 response, limiting parasitic growth. However, little is known about how cysticerci respond to an immunological environment in resistant mice. Here, we show that the Th1 response, during infection in resistant C57BL/6 mice, lasted up to 8 weeks and kept parasitemia low. Proteomics analysis of parasites during this Th1 environment showed an average of 128 expressed proteins; we chose 15 proteins whose differential expression varied between 70 and 100%. A total of 11 proteins were identified that formed a group whose expression increased at 4 weeks and decreased at 8 weeks, and another group with proteins whose expression was high at 2 weeks and decreased at 8 weeks. These identified proteins participate in tissue repair, immunoregulation and parasite establishment. This suggests that T. crassiceps cysticerci in mice resistant under the Th1 environment express proteins that control damage and help to establish a parasite in the host. These proteins could be targets for drugs or vaccine development.

Cu,Zn superoxide dismutase: cloning and analysis of the Taenia solium gene and Taenia crassiceps cDNA.

Cytosolic Cu,Zn superoxide dismutase (Cu,Zn-SOD) catalyzes the dismutation of superoxide (O(2)(-)) to oxygen and hydrogen peroxide (H(2)O(2)) and plays an important role in the establishment and survival of helminthes in their hosts. In this work, we describe the Taenia solium Cu,Zn-SOD gene (TsCu,Zn-SOD) and a Taenia crassiceps (TcCu,Zn-SOD) cDNA. TsCu,Zn-SOD gene that spans 2.841 kb, and has three exons and two introns; the splicing junctions follow the GT-AG rule. Analysis in silico of the gene revealed that the 5'-flanking region has three putative TATA and CCAAT boxes, and transcription factor binding sites for NF1 and AP1. The transcription start site was a C, located at 22 nucleotides upstream of the translation start codon (ATG). Southern blot analysis showed that TcCu,Zn-SOD and TsCu,Zn-SOD genes are encoded by a single copy. The deduced amino acid sequences of TsCu,Zn-SOD gene and TcCu,Zn-SOD cDNA reveal 98.47% of identity, and the characteristic motives, including the catalytic site and ß-barrel structure of the Cu,Zn-SOD. Proteomic and immunohistochemical analysis indicated that Cu,Zn-SOD does not have isoforms, is distributed throughout the bladder wall and is concentrated in the tegument of T. solium and T. crassiceps cysticerci. Expression analysis revealed that TcCu,Zn-SOD mRNA and protein expression levels do not change in cysticerci, even upon exposure to O(2)(-) (0-3.8 nmol/min) and H(2)O(2) (0-2mM), suggesting that this gene is constitutively expressed in these parasites.

Prognostic factors of trochanteric bursitis in surgical-staged patients: a prospective study.

BACKGROUND: Trochanteric bursitis or greater trochanteric pain syndrome is a common disorder and frequent cause of lateral hip pain. It can lead to severe functional impairment with increase morbidity and poor quality of life.The purpose of the current study was to identify and evaluate relationship between health-related factors, as prognostic indicators, and clinical outcomes. METHODS: A single-centre, prospective study was conducted and 60 patients (62 hips) were included with a minimum 12 months of follow-up. Clinical outcomes were evaluated using Hip Outcome Scale, Single Assessment Numeric Evaluation and Visual Analogue Scale. Radiological assessments and health-related factors were documented in an attempt to understand their validity as predictors of clinical outcomes. Complications and recurrence rates were also analyzed. RESULTS: Univariate model revealed that an increased BMI (p = 0.001; OR = 1.05; 95% CI, 1.02-1.07); number of previous corticosteroid infiltrations (p = 0.001; OR = 1.28, 95% CI, 1.11-1.48); longer time from symptom onset to surgery (p = 0.001; OR = 1.19; 95% CI, 1.12-1.28); smoker status (p = 0.001; OR 11.2; 95% CI, 3.30-44.2); and the presence of prior lumbosacral fusion (LSF) (p = 0.001; OR 13.8; 95% CI, 2.96-101); were prognostic factors predisposing for poor clinical outcomes.Among prognostic health-related factors were medical comorbidities such as emotional distress (p < 0.001; OR 26.1; 95% CI, 5.71-192); fibromyalgia (p = 0.026; OR 3.56; 95% CI, 1.16-11.7); and hyporthyroidism (p = 0.005, OR = 6.55, 95% CI, 1.73-28.7). CONCLUSIONS: Better overall physical function was predicted by lower number of corticosteroid infiltrations, shorter time span from symptom onset to surgery, non-smoker status and the absence of prior lumbosacral fusion. Obesity, smoking, the presence of emotional distress, fibromyalgia and hypothyroidism seem to increase the risk of poor clinical outcomes. A proper selection and/or correction of modifiable prognostic factors could reduce the incidence of endoscopic treatment failure and, as a consequence, improve patient outcomes and quality of life. However, future efforts should focus on experimental and randomised studies to fully determine these associations.

Prevalence and global estimates of unsafe listening practices in adolescents and young adults: a systematic review and meta-analysis.

INTRODUCTION: This study aimed to determine the prevalence of unsafe listening practices from exposure to personal listening devices (PLDs) and loud entertainment venues in individuals aged 12-34 years, and to estimate the number of young people who could be at risk of hearing loss from unsafe listening worldwide. METHODS: We conducted a systematic review and meta-analysis to estimate the prevalence of unsafe listening practices from PLDs and loud entertainment venues. We searched three databases for peer-reviewed articles published between 2000 and 2021 that reported unsafe listening practices in individuals aged 12-34 years. Pooled prevalence estimates (95% CI) of exposed populations were calculated using random effects models or ascertained from the systematic review. The number of young people who could be at risk of hearing loss worldwide was estimated from the estimated global population aged 12-34 years, and best estimates of exposure to unsafe listening ascertained from this review. RESULTS: Thirty-three studies (corresponding to data from 35 records and 19 046 individuals) were included; 17 and 18 records focused on PLD use and loud entertainment venues, respectively. The pooled prevalence estimate of exposure to unsafe listening from PLDs was 23.81% (95% CI 18.99% to 29.42%). There was limited certainty (p>0.50) in our pooled prevalence estimate for loud entertainment venues. Thus, we fitted a model as a function of intensity thresholds and exposure duration to identify the prevalence estimate as 48.20%. The global estimated number of young people who could be at risk of hearing loss from exposure to unsafe listening practices ranged from 0.67 to 1.35 billion. CONCLUSIONS: Unsafe listening practices are highly prevalent worldwide and may place over 1 billion young people at risk of hearing loss. There is an urgent need to prioritise policy focused on safe listening. The World Health Organization provides comprehensive materials to aid in policy development and implementation.