Pseudouridylation defect due to DKC1 and NOP10 mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis.

RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), NOP10, NHP2, and GAR1. Mutations in DKC1, NOP10, or NHP2 cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with DKC1 p.Glu206Lys and two children with homozygous NOP10 p.Thr16Met. Females with heterozygous DKC1 p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin-NOP10 binding interface in a region distinct from those implicated in DC, impair the dyskerin-NOP10 interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafish dkc1 mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction.

Recursive splicing in long vertebrate genes.

It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an 'RS-exon' that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5' splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5' splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons.

Structural and functional conservation of non-lumenized lymphatic endothelial cells in the mammalian leptomeninges.

The vertebrate CNS is surrounded by the meninges, a protective barrier comprised of the outer dura mater and the inner leptomeninges, which includes the arachnoid and pial layers. While the dura mater contains lymphatic vessels, no conventional lymphatics have been found within the brain or leptomeninges. However, non-lumenized cells called Brain/Mural Lymphatic Endothelial Cells or Fluorescent Granule Perithelial cells (muLECs/BLECs/FGPs) that share a developmental program and gene expression with peripheral lymphatic vessels have been described in the meninges of zebrafish. Here we identify a structurally and functionally similar cell type in the mammalian leptomeninges that we name Leptomeningeal Lymphatic Endothelial Cells (LLEC). As in zebrafish, LLECs express multiple lymphatic markers, containing very large, spherical inclusions, and develop independently from the meningeal macrophage lineage. Mouse LLECs also internalize macromolecules from the cerebrospinal fluid, including Amyloid-ß, the toxic driver of Alzheimer's disease progression. Finally, we identify morphologically similar cells co-expressing LLEC markers in human post-mortem leptomeninges. Given that LLECs share molecular, morphological, and functional characteristics with both lymphatics and macrophages, we propose they represent a novel, evolutionary conserved cell type with potential roles in homeostasis and immune organization of the meninges.

Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain.

Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, lrp6 mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain.

[Inclusive education in nursing: analysis of students' needs]. / Educação inclusiva em enfermagem: análise das necessidades de estudantes.

Inclusive education is based on assisting all students alike, providing an education aimed at everyone equally in order to identify the particular educational needs of each student. The objectives of the present study were to identify the occurrence of disabilities, explore the learning resources that allow for inclusion; identify the architectural, communication, educational and attitudinal barriers that may affect students' performance; and discuss the students' suggestions of how to promote inclusion. This exploratory, descriptive, cross-sectional study was performed using a quantitative approach. Data collection was performed through interviewing undergraduate nursing students, using a questionnaire containing open- and closed-ended questions. It was found that 66.3% of students have a visual impairment and 1.2% reported having a hearing impairment, but no physical disability was reported. Architectural barriers were the most frequently mentioned by the interviewed students, followed by educational barriers.

Kinematic analysis of the basketball jump shot with increasing shooting distance: comparison between experienced and non-experienced players.

PURPOSE: Basketball jump shot success is determined mainly by the height, velocity and angle of ball release. To achieve a successful shot, these variables need to be adjusted according to the player's position on the court. This study aimed to identify the changes in kinematics variables of the basketball jump shot with an increasing shooting distance performed by players with varying skill levels. METHODS: Seventeen male subjects, divided into experienced (N = 9), and non-experienced (N = 8) players, performed three successful jump shots from the free-throw line (4.23 m) and the 3-point line (6.75 m). All attempts were recorded at 120 Hz with a camera perpendicularly to the sagittal plane, and the kinematics variables were calculated using Tracker software. RESULTS: The increase in shooting distance shows a decrease in height and angle of ball release. In contrast, the velocity of ball release increased for both groups at longer distances. Experienced players presented a higher mean value of the height of ball release in both distances, which allowed for a lower velocity of ball release. CONCLUSIONS: The most meaningful improvement for players training the jump shot technique is to increase the release height of the ball, jumping higher and shooting the ball near the peak of the jump.

[Nursing allocation and adverse events/incidents in intensive care units]. / Alocação da equipe de enfermagem e ocorrência de eventos adversos/incidentes em unidade de terapia intensiva.

Patient safety is a challenge for the quality in health care system. This study aimed to analyze the appropriateness of the allocation of nursing staff according to the hours of care required by patients and to identify the relationship between this allocation and adverse events/incidents (EA/I). This research was observational, descriptive and prospective, developed in Clinics ICU located in the 4th floor and 6th floor at a university hospital, in São Paulo, Brazil, from 01/11/07 to 10/12/07, with 46 patients. In the 4th floor and 6th floor ICU, respectively, 43,3% and 10.3% of allocations were inadequate (p=0.000). There was a difference in the frequency of EA/I between the adequate and inadequate allocation of nursing staff in the 4th floor and 6th floor ICU, p=0.0004 and p=0.000, respectively. It was concluded that the greater the difference between available and required hours of care in nursing allocations, the lower the frequency of EA/I.

[Clean intermittent self catheterization in spinal cord injury]. / Autocateterismo vesical intermitente na lesão medular.

The clean intermittent self catheterization is an effective and safe technique for the treatment and prevention of urinary tract disease that result from spinal cord injuries. Although it has been described as of 1972, there is still resistance from health professionals for its utilization. The present study presents a report about the method used for training and encouraging of the patients towards using the technique, in a project of clinical and voluntary nursing care, performed in at a philanthropic association in the city of Curitiba. Our objective was to disseminate the experience that was learnt, to encourage professionals who assist people with spinal cord injuries towards recommending this technique.

[Nursing students' perception about the Nursing Laboratory as a teaching strategy]. / Percepção de estudantes de enfermagem sobre o Laboratório de Enfermagem como estratégia de ensino.

The objective of this study is to get to know the nursing students' perception in terms of the physical, educational and human aspects of the nursing laboratory in the teaching-learning process. This is a quantitative, cross-sectional, non-experimental study. Participants were 85 students who answered to a questionnaire about the laboratory in regard to human resources, teaching resources, physical infrastructure, and accommodation and hours of operation. Regarding the physical infrastructure of the lab, the majority of students (58.8%) rated it as bad or average, and accommodation was rated between bad and extremely bad by 50.6% of the students. The lab working hours were rated from good to excellent by 63.5% of the students. The nursing specialists and monitors of the laboratory were positively rated by the students, with 87.0% and 84.9% rating them from good to excellent, respectively. According to the students, the best aspect of the laboratory was human resources.

[Functional evaluation of aged with fractures at hospitalization and at home]. / Avaliação funcional de idoso vítima de fraturas na hospitalização e no domicílio.

Trauma is often related to functional impairment, representing an important social, economic and health issue. This study intended to evaluate the functional independence of aged individuals with fractures, at admission, discharge and after one month from their regressing home. Furthermore, this study also intended to verify the relationship between functional independence and demographic and health variables. Thirty-four aged individuals hospitalized at the Orthopedics and Traumatology Institute of the University of São Paulo Faculty of Medicine were interviewed and submitted to the application of the Functional Independence Measure (FIM). Among all fractures, 67.6% were femur fractures. The motor and total FIM scores increased at discharge; on the other hand, the total FIM score decreased one month after their returning home. Functional impairment increased with age and also with longer length of stay. Hypothyroidism was related to cognitive impairment, while dementia and depression were related to motor impairment.

Sox1a mediates the ability of the parapineal to impart habenular left-right asymmetry.

Left-right asymmetries in the zebrafish habenular nuclei are dependent upon the formation of the parapineal, a unilateral group of neurons that arise from the medially positioned pineal complex. In this study, we show that both the left and right habenula are competent to adopt left-type molecular character and efferent connectivity upon the presence of only a few parapineal cells. This ability to impart left-sided character is lost in parapineal cells lacking Sox1a function, despite the normal specification of the parapineal itself. Precisely timed laser ablation experiments demonstrate that the parapineal influences neurogenesis in the left habenula at early developmental stages as well as neurotransmitter phenotype and efferent connectivity during subsequent stages of habenular differentiation. These results reveal a tight coordination between the formation of the unilateral parapineal nucleus and emergence of asymmetric habenulae, ensuring that appropriate lateralised character is propagated within left and right-sided circuitry.

Physical exercise according to nursing students' perceptions.

This study aimed to get to know the perceptions of undergraduate students from the University of São Paulo College of Nursing about physical exercise as an instrument to maintain health and well being. Data were collected through the application of a questionnaire in class, involving 122 undergraduate students. In this group, 52.23% believed that physical exercise should only be recommended to people with health problems. Only 8% thought that exercise can prevent diseases, and only 6.61% uses protection equipment. Therefore, we concluded that nursing students need to be better prepared to be able to intervene correctly as professionals.

[Rehabilitation nursing: expanding horizons, legitimizing knowledge]. / Enfermagem em reabilitação: ampliando os horizontes, legitimando o saber.

The author makes reflections on Rehabilitation Nursing, marking the trajectory of this area in Nursing in terms of care, teaching and research. She discusses concepts and their applicability in Rehabilitation Nursing practice and presents the current demand for care in rehabilitation, as well as the capacity-building of nurses to work in this market, highlighting the pioneering initiatives of public institutions and higher education establishments in the city of São Paulo, which has made possible the specialization of nurses in Rehabilitation.

[Taking care of persons handicapped by cerebral vascular accident at home: the familial caregiver activity]. / Cuidar de pessoa incapacitada por acidente vascular cerebral no domicílio: o fazer do cuidador familiar.

An exploratory descriptive and quantitative study aimed at identifying and describing the activity of relatives in charge of caring at home for people incapacitated by cerebral vascular accident. The sample was comprised of 35 family caregivers, most of them women, wives or daughters. The care given is directly related to the degree of incapacity of the person who is being cared for. The orientation received indicated no commitment of professionals for the continuity of the care. The caregivers learn in daily practice how to care, based on observation and assistance to nursing during the internment period. The difficulties are related to physical effort, to lack of information and fear, to the embarassment and the shame of handling someone else's body. The study focuses on the need for preparation for hospital discharge, emphasizes the family as a concrete space for care; and observed an increase in life expectancy.

[The care of the nurse specialized in physical-motor rehabilitation]. / O cuidar do enfermeiro especialista em reabilitação físico-motora.

The main objective of the physical-motor rehabilitation process is to help people with physical deficiency adapt to their new condition of life. This paper aims to describe the activities developed by the rehabilitation nurse in a unit for patients undergoing physical-motor rehabilitation and to detail his/her importance for the rehabilitation team. Among the most important activities carried out are the maintenance of the patient's physiological needs, which the nursing staff executes, orients, demonstrates and supervises, and the reevaluation of the conditions of such patients to care for themselves. The nurse also acts in the prevention of possible complications that could occur given the unique susceptibility of this clientele.

The experience of nursing students facing death and dying.

OBJECTIVE: To understand the phenomenon experienced by nursing students in their academic practices in view of death and dying. METHODOLOGY: This was a qualitative study, based on Martin Heidegger' existential phenomenology, undertaken at a public University in Alagoas, Brazil, between August and October 2013. Seven senior students of nursing were interviewed. RESULTS: The phenomenological analysis yielded the following existential themes: Facing death and dying in academic practice; Acknowledging impotence in the face of death; Glimpsing the possibility of solicitude; Interacting with the family in view of the loss; Experiencing spirituality in the face of dying. CONCLUSION: It is deduced that, during the academic education, the theme involving death and dying has been addressed insufficiently, without precisely attending to all the demands of the nursing students during care in the dying process.

[Clean intermittent bladder autocatheterization: description of the procedure carried out by patients with spinal cord injuries]. / A técnica limpa do autocateterismo vesical intermitente: descrição do procedimento realizado pelos pacientes com lesão medular.

The present study describes the sequence and its materials used in the vesical autocatheterism intermittent--clean technique. The information were obtained together with the patients, who go through such procedure and were directed to follow the instructions, given by the inter disciplinary Service, attending patients with traumatic medullar injury. The study intends to contribute to increase the knowledge about the vesical autocatheterism and provide to the patients this technique in a therapeutic way.

[Nursing performance in an orthopedic and traumatology emergency service]. / ATUAÇÃO DE ENFERMAGEM EM UM PRONTO-SOCORRO DE ORTOPEDIA E TRAUMATOLOGÍA.

To determine the adequary of nursing assistance to population demand, the authors developed a brief survey of the actual physical area, nursing personnel, equipament and supply of the Orthopedic and Traumatology Emergency Service where the study is been done.

[Physiopathologic aspects and nursing care in the rehabilitation of subjects with spinal cord injury]. / Aspectos fisiopatológicos e assistenciais de enfermagem na reabilitação da pessoa com lesão medular.

Spinal cord injury can cause neurological damage such as alterations in the motor, sensitive and autonomic function. In this paper, details of clinical complications such as PVT, infection, respiratory insufficiency, pressure ulcers, autossomic disreflection, orthostatic hypotension, sphincteral-vesical and intestinal disfunctions, are related. And will also present prophylactic and therapeutic nursing care interventions designed for the well-being and improvement in life quality for patients.

Scales on Quality of Life in patients with spinal cord injury: integrative review.

Studies evaluating the Quality of Life of individuals with spinal cord injury using different research tools demonstrate that the Quality of Life scores are considered low both in national and international studies. The objective of this review was to characterize the international scientific production about the most used scales to assess Quality of Life in patients with spinal cord injury. We examined articles on Quality of Life of patients with spinal cord injury published over the last 5 years and indexed in the National Library of Medicine (PUBMED). During this period, 28 articles met the inclusion criteria. Eleven studies were conducted in the United States, five articles were published in Australia, and four in Canada. Brazil, France, Holland, India, Japan, Norway, Singapore and Switzerland contributed with one study each. The scientific articles were published in 13 high impact factor journals. Seven different instruments to assess Quality of Life were used in the studies: Satisfaction with Life Scale, Short Form (36) Health Survey, The Brief Version of the WHO Quality of Life Questionnaire (WHOQOL-BREF), Comprehensive Quality of Life Scale, Life Situation Questionnaire-Revised, Quality of Well-Being Scale and the SF-12® Health Survey. The articles examined underscore the impact of spinal cord injury in the Quality of Life of patients, demonstrating how this condition impairs their lives, mainly socially, but followed by the physical aspects. Despite the studies have different goals they all acknowledge that further studies are necessary in order to determine the Quality of Life of patients with spinal cord injury. Specific instruments should be chosen or developed and validated in order to fulfill this purpose.