Allele-dependent interaction of LRRK2 and NOD2 in leprosy.

Leprosy, caused by Mycobacterium leprae, rarely affects children younger than 5 years. Here, we studied a multiplex leprosy family that included monozygotic twins aged 22 months suffering from paucibacillary leprosy. Whole genome sequencing identified three amino acid mutations previously associated with Crohn's disease and Parkinson's disease as candidate variants for early onset leprosy: LRRK2 N551K, R1398H and NOD2 R702W. In genome-edited macrophages, we demonstrated that cells expressing the LRRK2 mutations displayed reduced apoptosis activity following mycobacterial challenge independently of NOD2. However, employing co-immunoprecipitation and confocal microscopy we showed that LRRK2 and NOD2 proteins interacted in RAW cells and monocyte-derived macrophages, and that this interaction was substantially reduced for the NOD2 R702W mutation. Moreover, we observed a joint effect of LRRK2 and NOD2 variants on Bacillus Calmette-Guérin (BCG)-induced respiratory burst, NF-κB activation and cytokine/chemokine secretion with a strong impact for the genotypes found in the twins consistent with a role of the identified mutations in the development of early onset leprosy.

Identification of biomarkers predictive of metastasis development in early-stage colorectal cancer using network-based regularization.

Colorectal cancer (CRC) is the third most common cancer and the second most deathly worldwide. It is a very heterogeneous disease that can develop via distinct pathways where metastasis is the primary cause of death. Therefore, it is crucial to understand the molecular mechanisms underlying metastasis. RNA-sequencing is an essential tool used for studying the transcriptional landscape. However, the high-dimensionality of gene expression data makes selecting novel metastatic biomarkers problematic. To distinguish early-stage CRC patients at risk of developing metastasis from those that are not, three types of binary classification approaches were used: (1) classification methods (decision trees, linear and radial kernel support vector machines, logistic regression, and random forest) using differentially expressed genes (DEGs) as input features; (2) regularized logistic regression based on the Elastic Net penalty and the proposed iTwiner-a network-based regularizer accounting for gene correlation information; and (3) classification methods based on the genes pre-selected using regularized logistic regression. Classifiers using the DEGs as features showed similar results, with random forest showing the highest accuracy. Using regularized logistic regression on the full dataset yielded no improvement in the methods' accuracy. Further classification using the pre-selected genes found by different penalty factors, instead of the DEGs, significantly improved the accuracy of the binary classifiers. Moreover, the use of network-based correlation information (iTwiner) for gene selection produced the best classification results and the identification of more stable and robust gene sets. Some are known to be tumor suppressor genes (OPCML-IT2), to be related to resistance to cancer therapies (RAC1P3), or to be involved in several cancer processes such as genome stability (XRCC6P2), tumor growth and metastasis (MIR602) and regulation of gene transcription (NME2P2). We show that the classification of CRC patients based on pre-selected features by regularized logistic regression is a valuable alternative to using DEGs, significantly increasing the models' predictive performance. Moreover, the use of correlation-based penalization for biomarker selection stands as a promising strategy for predicting patients' groups based on RNA-seq data.

Conradi-Hünerman-Happle Syndrome and Obsessive-Compulsive Disorder: a clinical case report.

BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a common and chronic psychiatric disorder with significant morbidity characterized by intrusive, uncontrollable and reoccurring thoughts (i.e., obsessions) and/or ritualistic behaviours (i.e., compulsions). Conradi-Hünerman-Happle Syndrome (CHHS) is a rare inherited X-linked dominant variant of chondrodysplasia punctata, a heterogeneous group of rare bone dysplasias characterized by punctate epiphyseal calcifications of complex etiology and pathophysiology that remain to be defined. Available literature reveals a lacuna in regards to the coexistence of the entities with no clinical reports described. CASE PRESENTATION: A 12 year old female patient with diagnosis of CHHS, presents to psychiatric consultation due to aggravation of her OCD clinical picture, with aggravation of hand-washing frequency during the Covid-19 pandemic with significant functional impact. Psychopharmacological treatment aimed at OCD with Selective Serotonin Reuptake Inhibitor (SSRI) and antipsychotic was instituted with favourable, albeit partial response. CONCLUSIONS: The authors aim to describe a clinical case in which the patient presents with Conradi-Hünerman-Happle Syndrome and Obsessive-Compulsive Disorder. Clinical descriptions of CHHS and OCD are not available in the literature. Through this case description the authors aim to present a rare case as well as discuss an eventual association between etiology and/or pathophysiology of the two disorders.

Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma.

AIM: Evaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy. BACKGROUND: Anemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes. MATERIALS AND METHODS: Retrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5 g/dL or <12.5 g/dL) at the beginning of cCRT with overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: A total of 108 patients were identified. With a median follow-up of 16.10 months median OS was 59.70 months for Hb ≥12.5 g/dL vs. 14.13 months for Hb <12.5 g/dL (p = 0.004). PFS was 12.29 months for Hb ≥12.5 g/dL and 1.68 months for Hb <12.5 g/dL (p = 0.016). CONCLUSIONS: In this analysis, Hb ≥12.5 g/dL correlated with significantly better OS and PFS. Further studies are needed to validate these findings.

Levels of Circulating Fibroblast Growth Factor 23 (FGF23) and Prognosis in Cancer Patients with Bone Metastases.

The fibroblast growth factor (FGF) signaling pathway plays a key role in tumorigenesis and is recognized as a potential therapeutic target. In this study, the authors aimed to assess the impact of serum FGF23 levels in the prognosis of patients with cancer and bone metastases from solid tumors. A cohort of 112 patients with cancer and metastatic bone disease were treated with bone-targeted agents (BTA). Serum baseline FGF23 was quantified by ELISA and dichotomized in FGF23high and FGF23low groups. Additionally, the association between FGF23 and overall survival (OS) and time to skeletal-related events (TTSRE) was investigated. Baseline characteristics were balanced between groups, except for the median urinary N-terminal telopeptide (uNTX) level. After a median follow-up of 26.0 months, a median OS of 34.4 and 12.2 months was found in the FGF23low and FGF23high groups, respectively (multivariate HR 0.18, 95% CI 0.07⁻0.44, p = 0.001; univariate HR 0.27, p = 0.001). Additionally, TTSRE was significantly longer for patients with FGF23low (13.0 vs 2.0 months, p = 0.04). Overall, this study found that patients with FGF23low at baseline had longer OS and TTSRE. Further studies are warranted to define its role as a prognostic biomarker and in the use of drugs targeting the FGF axis.

Discharge Planning After Myocardial Revascularization: Differences in Opinions From Patients and Health Experts.

BACKGROUND: In-hospital education and discharge planning contribute to recovery after coronary artery bypass graft surgery (CABG). OBJECTIVE: The objective of this study was to identify differences in perception of the importance of discharge instructions between a sample of adult patients after CABG and health experts responsible for their care. METHODS: Thirty-five first-time CABG adult patients and 8 multidisciplinary experts rated a 46-item questionnaire of discharge education themes on a 3-point scale. Items were classified as most important if rated as "very important" by more than 85% of the participants in each group. RESULTS: Of the 31 items considered most important (reaching the 85% approval criteria), agreement between groups was reached for 15 (48%), whereas 11 (35%) items were selected only by the patients and 5 (16%) were selected only by the experts. CONCLUSIONS: The authors of this study demonstrate a difference in perception between patients and health experts regarding the importance of various discharge instructions. Better understanding areas of patient concern may improve discharge routines.

Stress, coping and burnout among Intensive Care Unit nursing staff: associated factors. / Estresse, coping e burnout da Equipe de Enfermagem de Unidades de Terapia Intensiva: fatores associados.

Objective To investigate emotional stress, coping and burnout among nursing staff and their association with biosocial factors and characteristics of work in Intensive Care Units (ICU). Method This was a cross-sectional study, conducted in eight ICUs at a teaching hospital in the city of São Paulo, Brazil, in October 2012. Biosocial data and information about the professionals' work was gathered, and they were given the Scale of Occupational Stress, Scale of Occupational Coping, List of Signs and Symptoms of Stress and the Maslach Burnout Inventory. Results The study sample consisted of 287 subjects, predominately women, with partners and children. Most professionals presented moderate stress levels and control as a coping strategy (74.47% and 79.93%, respectively), and burnout was present among 12.54%. Factors associated with stress were related to working conditions. The most prevalent protective factors were having a partner, working in the clinical ICU and liking work, while adequate amount of sleep was a protective factor for burnout. Conclusion Control of the working environment and adequate sleep are decisive and protective factors in dealing with situations of occupational stress.

Hardy personality and burnout syndrome among nursing students in three Brazilian universities-an analytic study.

BACKGROUND: Nursing students may exhibit the characteristics of resistance to stress, such as hardiness, which can reduce the risk of burnout. However, we found only one published study about these phenomena among nursing students. Thus, we investigated the association between hardiness and burnout in such students. METHODS: An analytic, cross-sectional study was conducted among 570 nursing students from three Brazilian universities. Data were collected relating to sociodemographic characteristics, hardiness, and burnout, which we analyzed using inferential statistics. RESULTS: We observed that 64.04% of nursing students in the sample had a high level of emotional exhaustion, 35.79% had a high level of cynicism, and 87.72% had a low level of professional efficacy: these are dimensions of burnout. We also found that 48.77% had a high level of control, 61.40% a high level of commitment, and 35.44% a high level of challenge: these are dimensions of hardiness. Only 24.74% of the students experienced burnout, and 21.93% met the criteria for a hardy personality. There was a statistically significant difference between the frequency of hardiness and burnout (p = 0.033), with 68.00% of hardy students not exhibiting burnout. CONCLUSIONS: Although nursing students live with educational stressors, burnout was not preponderant in our sample students; this may be linked to hardiness. Thus, given its benefits to student life and health, we recommend the development of strategies to promote hardiness among nursing students.

[Influence of stress factors and socio-demographic characteristics on the sleep quality of nursing students]. / Influencia de los factores de estrés y de las características sociodemograficas en la calidad del sueño de estudiantes de enfermería.

OBJECTIVE: To analyze the influence of stress factors and socio-demographic characteristics on the sleep quality of nursing students. METHOD: An analytical cross-sectional and quantitative study, conducted with 151 nursing students in São Paulo between March and April of 2012. A form for socio-demographic characteristics, the Instrument to Evaluate Stress in Nursing Students and the Pittsburgh Sleep Index were applied. RESULTS: High levels of stress was predominant for Time Management (27.8%) and Professional Training (30.5%) and low sleep quality (78.8%). The Professional Communication, Professional Training and Theoretical Activity are positively correlated to sleep quality. Work activity, academic year and time for daily studies contributed to a low quality of sleep. CONCLUSION: Few stress factors from the academic environment and some socio-demographic characteristics contributed to the reduction of sleep quality in students.

[Subjective memory complain in healthy elderly: influence of depressive symptoms, perceived stress and self-esteem]. / Queixa subjetiva de comprometimento da memória em idosos saudáveis: influência de sintomas depressivos, percepção de estresse e autoestima.

The current study analyzed the relationship between perceived stress, depressive symptoms and self-esteem in elderly with and without subjective memory complain. Two-hundred four elderly were included (104 without and 100 with subjective memory complain) assesse using the Memory Assessment Complain Questionnaire (MAC-Q). The study protocol was composed by the Perceived Stress Scale (PSS), the Geriatric Depression Scale (GDS) and the Self-Esteem Scale of Rosenberg (SES). The elderly with subjective memory complain showed higher PSS and GDS scores (p < 0.001) and lower SES scores (p = 0.045). Negative correlation was observed between MAC-Q and PSS (p < 0.001) and GDS (p = 0.01). Multiple regression analysis showed predictor effect of perceived stress in the subjective memory complain. These findings suggest that the perceived stress and depressive symptoms are associated with subjective memory complain in elderly.

[Victims of traffic occurrence submitted to surgery procedures: characteristics and perioperative complications]. / Vítimas de ocorrência de trânsito submetidas a procedimentos cirúrgicos: características e intercorrências transoperatórias.

This study aimed to characterize the victims of traffic occurrence submitted to anesthetic-surgical procedures according to demographics and clinical data and identify the predictors of complications during the perioperative period (hemorrhagic shock and death). A cross-longitudinal analysis developed from the consultations of patients´ records submitted to surgery at a hospital in São Paulo city. There was predominance of young, male, and motorcycle/cyclist accident victims who received prehospital support in 69 analyzed patients. The abdomen as the most severely injured region, Injury Severity Score, general and orthopedic surgeries variables showed statistically significant association with shock and death. Age was only associated with shock. In the final model, the Injury Severity Score was predictor for shock and death, and general surgery only for shock. Orthopedic surgery was a protection factor for death. These findings subsidize the surgical team in strategic planning that aims to decrease undesirable outcomes.

[Education in operating room nursing: transformation of the discipline at University of São Paulo School of Nursing (Brazil)]. / Ensino de enfermagem em centro cirúrgico: transformações da disciplina na Escola de Enfermagem da USP (Brasil).

The objectives of this paper are to present a summary of the evolution of the content of perioperative nursing at the University of São Paulo School of Nursing (EEUSP) and reflect on the National Curriculum Directives (NCD) for the nursing course. The study was developed from a brief history of the practice of perioperative nursing and the inclusion of this topic in the nursing curriculum at EEUSP. The National Curriculum Directives are important because they permit undergraduate schools to determine the amount of teaching time for each course that will comprise their curriculum, but the competencies and skills proposed are nonspecific. We believe that the general nurse should have theoretical and practical learning opportunities to work in every area and level of healthcare.

Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development.

Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.

HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome.

Colorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P < 0.001). Combing NGS-based biomarkers (hERV/CD8 status) with clinicopathological factors provided a better prediction of patient survival compared to clinicopathological factors alone. Moreover, we explored the association between genomic and transcriptomic features of tumors with high hERV expression and establish this subtype as distinct from previously described consensus molecular subtypes of CRC. Overall, our results underscore a previously unknown role for hERVs in leading to a more aggressive subtype of CRC.

Grid-based International Network for Flu observation (g-INFO).

The 2009 H1N1 outbreak has demonstrated that continuing vigilance, planning, and strong public health research capability are essential defenses against emerging health threats. Molecular epidemiology of influenza virus strains provides scientists with clues about the temporal and geographic evolution of the virus. In the present paper, researchers from France and Vietnam are proposing a global surveillance network based on grid technology: the goal is to federate influenza data servers and deploy automatically molecular epidemiology studies. A first prototype based on AMGA and the WISDOM Production Environment extracts daily from NCBI influenza H1N1 sequence data which are processed through a phylogenetic analysis pipeline deployed on EGEE and AuverGrid e-infrastructures. The analysis results are displayed on a web portal (http://g-info.healthgrid.org) for epidemiologists to monitor H1N1 pandemics.

Health alterations in nursing students after a year from admission to the undergraduate course.

OBJECTIVE: To identify health alterations in nursing students after a year from admission to a nursing undergraduate course. METHOD: A longitudinal prospective study with a quantitative approach was carried out in 2016 with first-year nursing students from two universities in the state of São Paulo. The following instruments were applied at the beginning and the end of the first school year: an instrument for Assessment of Stress in Nursing Students, the Center for Epidemiologic Studies Depression Scale, and the Pittsburgh Sleep Quality Index. The ANOVA test for mixed models was used for analysis. RESULTS: The sample was made up of 117 students in March and 100 students in December. A significant increase in stress in all dimensions of the instrument, a reduction in the duration and subjective quality of sleep, and an increase in general stress and depressive symptoms were observed. CONCLUSION: The nursing academic environment presents the potential for students to become ill. Institutions should rethink their curricular elements, promote resilience, and create spaces to promote students' health.

Comparison of stress in freshman and senior nursing students.

OBJECTIVE: To compare stress levels in freshman and senior nursing students. METHOD: A cross-sectional study was carried out in a public federal university of the state of Bahia, with students who answered questionnaires about sociodemographic variables, academic life, and a scale for assessing stress in nursing students. Chi-square and Fisher's exact tests were applied to analyze the relationship between variables. To assess proportional trends between ordinal variables and groups, a chi-square test for linear trend was applied. The significance level was 5%. RESULTS: One hundred and fifty-four students participated in the study. There was a tendency to higher stress levels among students in the last year compared to those in the first year, in four out of six domains: Performance of Practical Activities (p=0.00), Professional Communication (p=0.00), Environment (p=0.00) and Professional Education (p=0.00). CONCLUSION: High levels of stress were observed in students taking the last year. There is a need for broader research that includes other years of the course, an institutional reflection on stress factors and the adoption of an institutional policy that favors a better confrontation of stress factors.

Relationship between cortisol reactivity to psychosocial stress and declarative memory decline during aging: Impact of age and sex.

AIM: To analyze the relationship between memory performance and the neuroendocrine and cardiovascular response to acute psychosocial stress in healthy older people, and the sex and age impact in this relationship. METHODS: We randomly selected 100 literate older adults, without cognitive or functional impairment. The neuroendocrine stress response was evaluated by measuring the concentration of salivary cortisol, whereas cardiovascular reactions were determined based on blood pressure and heart rate measures taken before, during and after participant exposure to an acute psychosocial stressor (the Trier social stress test [TSST]). Memory performance was evaluated by applying the word pairs test before and after the TSST. RESULTS: A significant reduction in the word pair test scores was observed after the TSST, and a negative correlation between cortisol concentration and immediate and delayed recall of the word pair. Cortisol concentration associated with age, sex and education explained memory performance variability before and after the TSST. CONCLUSIONS: The results showed that the influence of acute stress on memory performance during aging might vary according to age and sex, highlighting potential differences in the vulnerability of older individuals to the neurotoxic effects of stress exposure on memory and consequently on the development of cognitive disorders. Geriatr Gerontol Int 2018; 18: 169-176.

Short version of the "instrument for assessment of stress in nursing students" in the Brazilian reality.

GOAL: validate a short version of the Instrument for assessment of stress in nursing students in the Brazilian reality. METHOD: Methodological study conducted with 1047 nursing students from five Brazilian institutions, who answered the 30 items initially distributed in eight domains. Data were analyzed in the R Statistical Package and in the latent variable analysis, using exploratory and confirmatory factor analyses, Cronbach's alpha and item-total correlation. RESULTS: The short version of the instrument had 19 items distributed into four domains: Environment, Professional Training, Theoretical Activities and Performance of Practical Activities. The confirmatory analysis showed absolute and parsimony fit to the proposed model with satisfactory residual levels. Alpha values ​​per factor ranged from 0.736 (Environment) to 0.842 (Performance of Practical Activities). CONCLUSION: The short version of the instrument has construct validity and reliability for application to Brazilian nursing undergraduates at any stage of the course.

Biosocial-academic profile and stress in first- and fourth-year nursing students.

OBJECTIVES: To compare the biosocial and academic profile and stress levels between first- and last-year nursing students from a public university in Sao Paulo. METHODS: This is an analytic and quantitative study. A biosocial and academic form and the instrument for Assessment of Stress in Nursing Students by Costa and Polak were applied to 83 students between February and March 2016. RESULTS: Insufficient income and extracurricular activities contribute to higher levels of stress in both groups of students assessed. Fourth-year students showed higher levels of general stress, particularly generated by the factors: performance of practical activities, professional communication, environment and professional training. Time management produces higher stress in first-year students. CONCLUSIONS: Fewbiosocial and academic features equally contribute for the stress levels in first- and last-year nursing students, but those in last-year present higher stress than students who are starting the course.