Experience of patients undergoing liver transplantation during the covid-19 pandemic / Experiencia del patients sometido a trasplante hepático durante la pandemia de covid-19 / Vivência do paciente submetido ao transplante hepático durante a pandemia da covid-19

ABSTRACT Objective: to understand the experience of patients undergoing liver transplantation during the COVID-19 pandemic. Method: exploratory and qualitative research, developed in a reference hospital in liver transplantation, in the city of Florianópolis, Brazil. Participants were liver transplant patients between the years 2011 and 2021. Data collection conducted through a semi-structured script and data analysis performed according to content analysis. Results: from the participation of 23 patients, two categories of analysis emerged: "Perceptions about social isolation", with results related to coping and feelings related to social isolation; and "Actions and information: patients, support network and health services", revealing the meanings of strategies and changes developed in life activities of daily living as well as challenges faced with information and health services during the pandemic period. Conclusion: the study was able to understand liver transplant patients' experience in the face of the challenges they face during the pandemic. It allowed to visualize coping strategies, feelings and meanings based on recipients' perspective. As a contribution, it presents possibilities for achieving improvements in services and attention to weaknesses in health services, providing opportunities for reflections to improve this care and considering the specificities and complexities of the postoperative period of liver transplantation.

RESUMEN Objetivo: comprender la experiencia de los pacientes sometidos a trasplante hepático en la pandemia de COVID-19. Método: investigación exploratoria, con abordaje cualitativo, desarrollada en un hospital de referencia para trasplante hepático, en la ciudad de Florianópolis, Brasil. Los participantes fueron pacientes trasplantados de hígado entre los años 2011 y 2021. La recolección de datos se realizó a través de un guión semiestructurado y el análisis de datos se realizó de acuerdo con el análisis de contenido. Resultados: de la participación de 23 pacientes surgieron dos categorías de análisis: "Percepciones sobre el aislamiento social", con resultados relacionados al afrontamiento y sentimientos relacionados al aislamiento social; y "Acciones e información: paciente, red de apoyo y servicios de salud", revelando los significados de las estrategias y cambios desarrollados en las actividades de la vida diaria, así como los desafíos enfrentados con la información y los servicios de salud durante el período de la pandemia. Conclusión: el estudio logró comprender la experiencia de los pacientes trasplantados de hígado frente a los desafíos que enfrentan durante la pandemia. Permitido visualizar estrategias de afrontamiento, sentimientos y significados basados ​​en la propia perspectiva del receptor. Como aporte, presenta posibilidades para lograr mejoras en los servicios y atención a las debilidades de los servicios de salud, brindando espacios de reflexión para mejorar esa atención, considerando las especificidades y complejidades del postoperatorio del trasplante hepático.

RESUMO Objetivo: compreender a vivência do paciente submetido ao transplante hepático na pandemia da COVID-19. Método: pesquisa exploratória, de abordagem qualitativa desenvolvida em hospital de referência em transplante hepático, na cidade de Florianópolis, Brasil; os participantes foram pacientes transplantados hepáticos entre os anos de 2011 e 2021. Coleta de dados conduzida por meio de roteiro semiestruturado e análise dos dados realizada conforme análise de conteúdo. Resultados: da participação dos 23 pacientes, duas categorias de análise emergiram: "percepções acerca do isolamento social" com resultados relacionados aos enfrentamentos e sentimentos referentes ao isolamento social e "e "ações e informações: paciente, rede de apoio e serviços de saúde" desvelando os significados das estratégias e mudanças desenvolvidas nas atividades de vida diária bem como os desafios em face das informações e dos serviços de saúde durante o período da pandemia. Conclusão: o estudo foi capaz de compreender a vivência dos pacientes transplantados hepáticos ante os desafios enfrentados por eles durante a pandemia. Permitiu visualizar estratégias de enfrentamento, sentimentos e significados com base na perspectiva do próprio receptor. Como contribuição, apresenta possibilidades de alcance de melhorias nos serviços e de atenção às fragilidades dos serviços de saúde, oportunizando reflexões para a melhoria desse cuidado, considerando as especificidades e complexidades do pós-operatório do transplante hepático.

Sexual dimorphism in the width of the mouse synaptonemal complex.

Sexual dimorphism has been used to describe morphological differences between the sexes, but can be extended to any biologically related process that varies between males and females. The synaptonemal complex (SC) is a tripartite structure that connects homologous chromosomes in meiosis. Here, aided by super-resolution microscopy techniques, we show that the SC is subject to sexual dimorphism, in mouse germ cells. We have identified a significantly narrower SC in oocytes and have established that this difference does not arise from a different organization of the lateral elements nor from a different isoform of transverse filament protein SYCP1. Instead, we provide evidence for the existence of a narrower central element and a different integration site for the C-termini of SYCP1, in females. In addition to these female-specific features, we speculate that post-translation modifications affecting the SYCP1 coiled-coil region could render a more compact conformation, thus contributing to the narrower SC observed in females.

Multifocus structured illumination microscopy for fast volumetric super-resolution imaging.

We here report for the first time the synergistic implementation of structured illumination microscopy (SIM) and multifocus microscopy (MFM). This imaging modality is designed to alleviate the problem of insufficient volumetric acquisition speed in super-resolution biological imaging. SIM is a wide-field super-resolution technique that allows imaging with visible light beyond the classical diffraction limit. Employing multifocus diffractive optics we obtain simultaneous wide-field 3D imaging capability in the SIM acquisition sequence, improving volumetric acquisition speed by an order of magnitude. Imaging performance is demonstrated on biological specimens.

High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation.

During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.

The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during Caenorhabditis elegans Meiosis.

Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to the structural maintenance of chromosome (SMC) family and is closely related to cohesin and condensin. Although the Smc5/6 complex has been implicated in the processing of recombination intermediates during meiosis, it is not known how Smc5/6 controls meiotic DSB repair. Here, using Caenorhabditis elegans we show that the SMC-5/6 complex acts synergistically with HIM-6, an ortholog of the human Bloom syndrome helicase (BLM) during meiotic recombination. The concerted action of the SMC-5/6 complex and HIM-6 is important for processing recombination intermediates, CO regulation and bivalent maturation. Careful examination of meiotic chromosomal morphology reveals an accumulation of inter-chromosomal bridges in smc-5; him-6 double mutants, leading to compromised chromosome segregation during meiotic cell divisions. Interestingly, we found that the lethality of smc-5; him-6 can be rescued by loss of the conserved BRCA1 ortholog BRC-1. Furthermore, the combined deletion of smc-5 and him-6 leads to an irregular distribution of condensin and to chromosome decondensation defects reminiscent of condensin depletion. Lethality conferred by condensin depletion can also be rescued by BRC-1 depletion. Our results suggest that SMC-5/6 and HIM-6 can synergistically regulate recombination intermediate metabolism and suppress ectopic recombination by controlling chromosome architecture during meiosis.

Edentulismo, uso de prótese e autopercepção de saúde bucal entre idosos / Edentulism, denture wearing and self-perceived of oral health among elderly

Objetivo: O objetivo deste estudo foi verificar se a autopercepção de saúde bucal dos idosos apresenta coerência com a sua condição bucal, verificada a partir de exame de inspeção bucal, considerando perdas dentárias, uso e necessidade de próteses. Material e método: Participaram 103 voluntários que frequentam o Centro de Referência de Idosos da Fundação Pró-Família de Blumenau-SC. Os dados foram coletados através de exame de inspeção bucal e aplicação do questionário que compõe o índice Geriatric Oral Health Assesment Index (GOHAI). Resultado: Verificou-se maioria (83,5%) de mulheres entre os participantes, com média de idade de 70 anos. O edentulismo é alto, com 91,3% de usuários de prótese e 53,3% com necessidade de algum tipo de prótese. O valor médio do Índice de GOHAI, no grupo geral, foi 29,22, classificado como uma autopercepção de saúde bucal "ruim". Entre os homens e os portadores de dentes naturais, a condição bucal foi considerada "regular", com valores 31,3 e 31,7, respectivamente. Conclusão: A autopercepção de saúde bucal pode ser considerada coerente com a precária condição bucal encontrada, marcada por alta prevalência de dentes perdidos. A reabilitação protética não contribuiu para a melhora da autopercepção de saúde bucal. Esses dados devem orientar o planejamento dos serviços de saúde bucal para a promoção de saúde e o autocuidado. .

Aim: The aim of this study was to verify whether self-perceived of oral health among elderly shows consistency with their oral condition, verified from the examination of oral inspection, considering tooth loss, usage and necessity of dentures. Material and method: 103 volunteers who attend the Reference Center for Seniors Foundation Pro-Family Blumenau-SC participated. Data were collected through oral examination and questionnaire that composes the Geriatric Oral Health Assessment Index (GOHAI). Result: Most of participants was women (83.5%) with 70 years old in average. Edentulism is high with 91.3% users of dental prostheses and 53.3% needing some type of prosthesis. The average value of the GOHAI index in the general group was 29.22, classified as "bad" self-perceived of oral health. Among men and those with natural teeth oral condition was considered "regular" with values 31.3 and 31.7, respectively. Conclusion: The self-perceived of oral health can be considered consistent with poor oral condition found, marked by high prevalence of missing teeth. The prosthetic rehabilitation did not contribute to the improvement of self-perceived oral health. These data should guide the planning of oral health services to promote health and self-care. .

Looking out for cancer stem cells' properties: the value-driving role of CD44 for personalized medicines.

The expression of CD44 tags cells with stemness-associated properties (cancer initiating cells or cancer stem cells - CSC). This membrane glycoprotein with a cytoplasmic domain indirectly associated with the cellular cytoskeleton, has a crucial role in tumorigenesis. The CD44 receptor enables the cell to respond to changes in tumor microenvironment, promoting several signaling events related to tumor initiation, progression and fixation in distant host tissues. Although the contribution of this transmembrane protein in gene regulation remains unclear, its overexpression in adenocarcinomas, mostly supported by microRNA (miR)-mediated upregulation of target mRNA, is widely accepted. Herein, we gather the evidence that CD44 is one of the most predominant markers of malignant cells and may be found in diverse phenotypes associated with tumor progression. Additionally, CD44 tumor receptors were found to have different roles at a transcriptional level. Thus, innovative therapeutic strategies should rely heavily on its metastasis-promoting ability. Furthermore, the concept of selectively targeting cell sub-populations may be used to develop specific therapeutic and/or diagnostic systems. An approach based on targeting CD44⁺ cells might provide a strategy to design guided-therapeutic systems against multiple malignant cells including putative CSC.

Dynamic SUMO modification regulates mitotic chromosome assembly and cell cycle progression in Caenorhabditis elegans.

The small ubiquitin-like modifier (SUMO), initially characterized as a suppressor of a mutation in the gene encoding the centromeric protein MIF2, is involved in many aspects of cell cycle regulation. The dynamics of conjugation and deconjugation and the role of SUMO during the cell cycle remain unexplored. Here we used Caenorhabditis elegans to establish the contribution of SUMO to a timely and accurate cell division. Chromatin-associated SUMO conjugates increase during metaphase but decrease rapidly during anaphase. Accumulation of SUMO conjugates on the metaphase plate and proper chromosome alignment depend on the SUMO E2 conjugating enzyme UBC-9 and SUMO E3 ligase PIAS(GEI-17). Deconjugation is achieved by the SUMO protease ULP-4 and is crucial for correct progression through the cell cycle. Moreover, ULP-4 is necessary for Aurora B(AIR-2) extraction from chromatin and relocation to the spindle mid-zone. Our results show that dynamic SUMO conjugation plays a role in cell cycle progression.

STAG3-mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis.

Cohesion between sister chromatids in mitotic and meiotic cells is promoted by a ring-shaped protein structure, the cohesin complex. The cohesin core complex is composed of four subunits, including two structural maintenance of chromosome (SMC) proteins, one α-kleisin protein, and one SA protein. Meiotic cells express both mitotic and meiosis-specific cohesin core subunits, generating cohesin complexes with different subunit composition and possibly separate meiotic functions. Here, we have analyzed the in vivo function of STAG3, a vertebrate meiosis-specific SA protein. Mice with a hypomorphic allele of Stag3, which display a severely reduced level of STAG3, are viable but infertile. We show that meiocytes in homozygous mutant Stag3 mice display chromosome axis compaction, aberrant synapsis, impaired recombination and developmental arrest. We find that the three different α-kleisins present in meiotic cells show different dosage-dependent requirements for STAG3 and that STAG3-REC8 cohesin complexes have a critical role in supporting meiotic chromosome structure and functions.

Combinatorial regulation of meiotic holliday junction resolution in C. elegans by HIM-6 (BLM) helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 nucleases.

Holliday junctions (HJs) are cruciform DNA structures that are created during recombination events. It is a matter of considerable importance to determine the resolvase(s) that promote resolution of these structures. We previously reported that C. elegans GEN-1 is a symmetrically cleaving HJ resolving enzyme required for recombinational repair, but we could not find an overt role in meiotic recombination. Here we identify C. elegans proteins involved in resolving meiotic HJs. We found no evidence for a redundant meiotic function of GEN-1. In contrast, we discovered two redundant HJ resolution pathways likely coordinated by the SLX-4 scaffold protein and also involving the HIM-6/BLM helicase. SLX-4 associates with the SLX-1, MUS-81 and XPF-1 nucleases and has been implicated in meiotic recombination in C. elegans. We found that C. elegans [mus-81; xpf-1], [slx-1; xpf-1], [mus-81; him-6] and [slx-1; him-6] double mutants showed a similar reduction in survival rates as slx-4. Analysis of meiotic diakinesis chromosomes revealed a distinct phenotype in these double mutants. Instead of wild-type bivalent chromosomes, pairs of "univalents" linked by chromatin bridges occur. These linkages depend on the conserved meiosis-specific transesterase SPO-11 and can be restored by ionizing radiation, suggesting that they represent unresolved meiotic HJs. This suggests the existence of two major resolvase activities, one provided by XPF-1 and HIM-6, the other by SLX-1 and MUS-81. In all double mutants crossover (CO) recombination is reduced but not abolished, indicative of further redundancy in meiotic HJ resolution. Real time imaging revealed extensive chromatin bridges during the first meiotic division that appear to be eventually resolved in meiosis II, suggesting back-up resolution activities acting at or after anaphase I. We also show that in HJ resolution mutants, the restructuring of chromosome arms distal and proximal to the CO still occurs, suggesting that CO initiation but not resolution is likely to be required for this process.

Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2.

DNA interstrand crosslinks (ICLs) are highly toxic because they block the progression of replisomes. The Fanconi Anemia (FA) proteins, encoded by genes that are mutated in FA, are important for repair of ICLs. The FA core complex catalyzes the monoubiquitination of FANCD2, and this event is essential for several steps of ICL repair. However, how monoubiquitination of FANCD2 promotes ICL repair at the molecular level is unknown. Here, we describe a highly conserved protein, KIAA1018/MTMR15/FAN1, that interacts with, and is recruited to sites of DNA damage by, the monoubiquitinated form of FANCD2. FAN1 exhibits endonuclease activity toward 5' flaps and has 5' exonuclease activity, and these activities are mediated by an ancient VRR_nuc domain. Depletion of FAN1 from human cells causes hypersensitivity to ICLs, defects in ICL repair, and genome instability. These data at least partly explain how ubiquitination of FANCD2 promotes DNA repair.

Padrão de prescrição de medicamentos as Unidades de Programa de Saúde da Família de Blumenau / Prescribed drugs in Attendance Sampling at Basic Health Service in Blumenau

Os medicamentos constituem parte importante dos recursos terapêuticos disponíveis e muitas vezes são a opção com melhor perfil custo-benefício. O conhecimento do padrão de prescrição de um determinado local possibilita melhor gerenciamento da assitência farmacêutica. O objetivo do presente trabalho foi descrever os medicamentos prescritos em uma amostragem do Programa de Saúde da Família (PSF) de Blumenau, SC. Foram entrevistados 186 pacientes durante um dia de atendimento, classificando-se dados de acordo com os indicadores de prescrição da OMS. Foram prescritos 336 medicamentos, sendo que o número médio de medicamentos por prescrição foi 1,8...