Hyperhidrosis and human leucocyte antigens in the Danish Blood Donor Study.

Familial clustering of the skin disease primary hyperhidrosis suggests a genetic component to the disease. The human leucocyte antigen (HLA) is implicated in a range of diseases, including many comorbidities to hyperhidrosis. No study has investigated whether the HLA genes are involved in the pathogenesis of hyperhidrosis. We, therefore, compared HLA alleles in individuals with and without hyperhidrosis in this study of 65 000 blood donors. In this retrospective cohort study, we retrieved information on individuals with and without hyperhidrosis using self-reported questionnaires, the Danish National Patient Registry and the Danish National Prescription Registry on participants recruited to the Danish Blood Donor Study between 2010 and 2019. Association tests using logistic regression were conducted for each HLA allele corrected for sex, age, body mass index, smoking and principal components. Overall, 145 of 65 795 (0.2%) participants had hospital diagnosed hyperhidrosis. Similarly, 1379 of 15 530 (8.9%) participants had moderate-severe self-reported hyperhidrosis, of whom 447 (2.9%) had severe self-reported hyperhidrosis. Altogether, 28 participants had both hospital diagnosed and moderate-severe self-reported hyperhidrosis. Severe self-reported hyperhidrosis was associated with HLA-A*80:01 (adjusted odds ratio 26.97; 95% confidence interval 5.32-136.70; n = 7; P < .001). Moderate-severe self-reported hyperhidrosis and hospital diagnosed hyperhidrosis were not associated with any HLA. The association between hyperhidrosis and HLA-A*80:01 was based on a very small number of cases and not replicated in other patient subsets, and therefore likely a chance finding. Thus, this study suggests that genes other than the HLA are involved in the pathogenesis of hyperhidrosis.

Ultrasound-guidance of peripheral venous catheterization in apheresis minimizes the need for central venous catheters.

INTRODUCTION: Central venous catheters (CVC) can facilitate a reliable blood flow for apheresis procedures, but the placement is time-consuming and costly and the incidence of catheter-related complications is high. Ultrasound can aid nurses to insert peripheral venous catheters (PVC), which is safer for the patients. METHODS AND MATERIALS: We evaluated the use of CVC vs PVC for all apheresis procedures 3 years after the implementation of structured training of apheresis nurses to perform ultrasound-guided PVC. Ultrasound can visualize the needle tip and target vessel dynamically and guide peripheral venous catheterization with an increased success rate. Time consumption for PVC insertion was measured. RESULTS: In 10 months, we performed 1294 apheresis procedures on 227 patients, where 97.4% were performed with PVC. Hundred percent of extracorporeal photophoresis (off-line ECP) and peripheral blood stem cell collections on adults were performed with PVC. Patients who were treated with CVC (n = 8) were either children, had poor peripheral blood flow due to dehydration or admitted to an intensive care unit and had CVC for other reasons. Time consumption for PVC placement with ultrasound was 11 minutes on average. CONCLUSION: Training of apheresis nurses in ultrasound-guided peripheral venous catheterization can enable close to 100% of apheresis procedures to be performed by PVC.

Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study.

Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71-4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.

The role of microRNAs 371 and 34a in androgen receptor control influencing prostate cancer behavior.

BACKGROUND: The molecular mechanisms involved in androgen receptor (AR) signaling pathways are not completely understood, and deregulation of microRNAs (miRNAs) expression may play a role in prostate cancer (PC) development and progression. METHODS: The expression levels of miRNA and AR were evaluated with quantitative real-time polymerase chain reaction using frozen tissue from the surgical specimens of 83 patients submitted to radical prostatectomy. The expression level of miRNAs was correlated with prognostic factors and biochemical recurrence during a follow-up period of 45 months. In vitro and in vivo experiments were performed to understand the effect of miRNAs over AR in the context of that seen in a PC model. RESULTS: MiR-371 underexpression correlated with non-organ-confined (pT3) disease (P = 0.009). In vitro transfection of miR-371 reduced the levels of AR by 22% and 28% in LNCaP and PC3 cell lines, respectively, and in kallikrein 3, it was reduced by 51%. PC was induced in Balb/c mice using PC-3M-luc-C6 cells, and animals were treated with 3 local doses of miR-371. Tumor growth evaluated by in vivo imaging after luciferase injection was slower in animals treated with miR-371. To explore further the possible role of miRNAs in the AR pathway, LNCaP cell line was treated with 5α-dihydrotestosterone and flutamide showing alteration in miRNAs expression, especially miR-34a, which was significantly underexpressed after treatment with high doses of 5α-dihydrotestosterone. CONCLUSION: Our data support a role for miRNAs, especially miR-371 and miR-34a, in the complex disarrangement of AR signaling pathway and in the behavior of PC.

Protein kinase C, focal adhesions and the regulation of cell migration.

Cell adhesion to extracellular matrix is a complex process involving protrusive activity driven by the actin cytoskeleton, engagement of specific receptors, followed by signaling and cytoskeletal organization. Thereafter, contractile and endocytic/recycling activities may facilitate migration and adhesion turnover. Focal adhesions, or focal contacts, are widespread organelles at the cell-matrix interface. They arise as a result of receptor interactions with matrix ligands, together with clustering. Recent analysis shows that focal adhesions contain a very large number of protein components in their intracellular compartment. Among these are tyrosine kinases, which have received a great deal of attention, whereas the serine/threonine kinase protein kinase C has received much less. Here the status of protein kinase C in focal adhesions and cell migration is reviewed, together with discussion of its roles and potential substrates.

Postoperative vomiting in pediatric oncologic patients: prediction by a fuzzy logic model.

OBJECTIVE: To report a fuzzy logic mathematical model to predict postoperative vomiting (POV) in pediatric oncologic patients and compare with preexisting scores. BACKGROUND: Although POV has a high incidence in children and may decrease parental satisfaction after surgeries, there is only one specific score that predicts POV in children: the Eberhart's score. In this study, we report a fuzzy model that intends to predict the probability of POV in pediatric oncologic patients. Fuzzy logic is a mathematical theory that recognizes more than simple true and false values and takes into account levels of continuous variables such as age or duration of the surgery. The fuzzy model tries to account for subjectiveness in the variables. METHODS: Preoperative potential risk factors for POV in 198 children (0-19 year old) with malignancies were collected and analyzed. Data analysis was performed with the chi-square test and logistic regression to evaluate probable risk factors for POV. A system based on fuzzy logic was developed with the risk factors found in the logistic regression, and a computational interface was created to calculate the probability of POV. RESULTS: The model showed a good performance in predicting POV. After the analysis, the model was compared with Eberhart's score in the same population and showed a better performance. CONCLUSIONS: The fuzzy score can predict the chance of POV in children with cancer with good accuracy, allowing better planning for postoperative prophylaxis of vomiting. The computational interface is available for free download at the internet and is very easy to use.

Quality of care, quality of life, and attitudes toward disabilities: perspectives from a qualitative focus group study in Porto Alegre, Brazil.

OBJECTIVE: To explore the concepts of quality of life (QOL), quality of care (QOC), and attitudes toward disabilities in Porto Alegre, Brazil, from the perspective of people living with disabilities, including their relatives and caregivers. METHODS: This was a qualitative study that interviewed a total of 23 participants in five focus groups, during May-August 2006. After an open discussion about QOL, the WHOQOL-Bref, a generic questionnaire for the assessment of QOL, was presented to participants. The study was performed simultaneously in 15 international centers. Analysis was based on Bardin's content analysis. RESULTS: Regarding QOL, important themes that emerged were: work, education, leisure, universal accessibility, integration in the society, and social inclusion. Concerning QOC, professional qualifications, disabilities-related training for health and education professionals, and access to health services were considered important. Regarding attitudes toward disabilities, the participants perceived the attitudes of others, especially of caregivers, to significantly impact the QOL of people with disabilities. CONCLUSIONS: People living with disabilities value many of the same themes considered important by the general public; however, several additional themes specific to disabilities and specific to these groups of participants emerged. This information highlights the importance of taking into account the unique perceptions and cultural traits of the target population when measuring QOL, QOC, and attitudes toward disabilities.

Quality of care, quality of life, and attitudes toward disabilities: perspectives from a qualitative focus group study in Porto Alegre, Brazil / Calidad de atención, calidad de vida y actitudes hacia la discapacidad: perspectivas de un estudio cualitativo con grupos de discusión en Porto Alegre, Brasil

OBJECTIVE: To explore the concepts of quality of life (QOL), quality of care (QOC), and attitudes toward disabilities in Porto Alegre, Brazil, from the perspective of people living with disabilities, including their relatives and caregivers. METHODS: This was a qualitative study that interviewed a total of 23 participants in five focus groups, during May-August 2006. After an open discussion about QOL, the WHOQOL-Bref, a generic questionnaire for the assessment of QOL, was presented to participants. The study was performed simultaneously in 15 international centers. Analysis was based on Bardin's content analysis. RESULTS: Regarding QOL, important themes that emerged were: work, education, leisure, universal accessibility, integration in the society, and social inclusion. Concerning QOC, professional qualifications, disabilities-related training for health and education professionals, and access to health services were considered important. Regarding attitudes toward disabilities, the participants perceived the attitudes of others, especially of caregivers, to significantly impact the QOL of people with disabilities. CONCLUSIONS: People living with disabilities value many of the same themes considered important by the general public; however, several additional themes specific to disabilities and specific to these groups of participants emerged. This information highlights the importance of taking into account the unique perceptions and cultural traits of the target population when measuring QOL, QOC, and attitudes toward disabilities.

OBJETIVO: Explorar los conceptos de calidad de vida, calidad de atención y actitudes hacia la discapacidad en Porto Alegre, Brasil, desde la perspectiva de las personas con discapacidad, incluidos los familiares y cuidadores del individuo discapacitado. MÉTODOS: En este estudio cualitativo se entrevistaron 23 participantes en cinco grupos de discusión entre mayo y agosto del 2006. Después de un debate abierto acerca de la calidad de vida, se presentó el WHOQOL-Bref, un cuestionario genérico empleado para su evaluación. El estudio se realizó simultáneamente en 15 centros internacionales. El análisis se basó en el análisis del contenido de Bardin. RESULTADOS: Respecto de la calidad de vida, los temas importantes que surgieron fueron el trabajo, la educación, el ocio, la accesibilidad universal, la integración en la sociedad y la inclusión social. Respecto de la calidad de atención, se consideraron importantes la formación profesional, la capacitación relacionada con la discapacidad en los profesionales de la educación y la salud y el acceso a los servicios de salud. Con respecto a las actitudes hacia la discapacidad, los participantes percibieron que las actitudes de los demás, en especial las de los cuidadores, repercuten significativamente en la calidad de vida de las personas con discapacidad. CONCLUSIONES: Las personas con discapacidad valoran muchos de los temas también considerados importantes por la población en general; sin embargo, surgieron varios otros temas específicos de la discapacidad y de estos grupos de participantes. Esta información destaca la importancia de tener en cuenta las percepciones y los rasgos culturales singulares de la población destinataria cuando se miden la calidad de vida, la calidad de atención y las actitudes hacia la discapacidad.

Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries.

For a CD8 epitope-based vaccine to match different geographic locations, the targeted epitopes for cytotoxic T-lymphocytes (CTLs) must be present in the local circulating HIV-1 strains. Secondly, the vaccine epitopes should match the host population HLA types. We characterized two new HIV-1 isolates from Guinea-Bissau. Also, we have identified 15 subdominant CD8 epitopes representing common HLA super-types theoretically covering most HLA alleles in any population. Herein we demonstrate that the selected vaccine epitopes are well conserved and simultaneously present in sequences from West Africa and Denmark. Use of the selected epitopes will likely ensure ≥10 immune targets in the majority of candidates for experimental therapeutic vaccination in both geographic regions. Our results warrant testing of the selected vaccine epitopes in both geographic locations.

RHD positive among C/E+ and D- blood donors in Denmark.

BACKGROUND: Many different partial and weak D types have been reported, and most of these are easily detected by serology. However, 17 Del types have also been described, with a very low expression of the D antigen, only detectable by absorption-elution techniques, and these may elicit the development of an anti-D. A genomic test of C/E+ and D- blood donors was initiated, to be able to categorize them correctly as D+ or -. STUDY DESIGN AND METHODS: We analyzed all C/E+ and D- donors within our donor population of 22,000 donors with an initial test for RHD Exon 10. In case of a positive reaction, the genotype was further analyzed by sequence-specific polymerase chain reaction or nucleotide sequencing of the RHD gene. CONCLUSIONS: Of 233 donors analyzed, seven were found positive for RHD Exon 10, and four of these were Del, corresponding to 1.7%. We report here a new mutation in the RHD gene. A correct assignment of all blood donors as D+ or D- is not possible using serotyping alone; genotyping offers the only exact categorization of all cases.

Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes.

OBJECTIVE: To investigate the potential to induce additional cytotoxic T-lymphocyte (CTL) immunity during chronic HIV-1 infection. DESIGN: We selected infrequently targeted or subdominant but conserved HLA-A*0201-binding epitopes in Gag, Pol, Env, Vpu and Vif. These relatively immune silent epitopes were modified as anchor-optimized peptides to improve immunogenicity and delivered on autologous monocyte-derived dendritic cells (MDDCs). METHODS: Twelve treatment-naïve HLA-A*0201 HIV-1-infected Danish individuals received 1 x 10 MDDCs subcutaneously (s.c.) (weeks 0, 2, 4 and 8), pulsed with seven CD8 T-cell epitopes and three CD4 T-cell epitopes. Epitope-specific responses were evaluated by intracellular cytokine staining for interferon-gamma, tumor necrosis factor alpha and interleukin-2 and/or pentamer labeling 3 weeks prior to, 10 weeks after and 32 weeks after the first immunization. RESULTS: Previously undetected T-cell responses specific for one or more epitopes were induced in all 12 individuals. Half of the participants had sustained CD4 T-cell responses 32 weeks after immunization. No severe adverse effects were observed. No overall or sustained change in viral load or CD4 T-cell counts was observed. CONCLUSION: These data show that it is possible to generate new T-cell responses in treatment-naive HIV-1-infected individuals despite high viral loads, and thereby redirect immunity to target new multiple and rationally selected subdominant CTL epitopes. Further optimization could lead to stronger and more durable cellular responses to selected epitopes with the potential to control viral replication and prevent disease in HIV-1-infected individuals.

Characterization of near full-length genomes of HIV type 1 strains in Denmark: basis for a universal therapeutic vaccine.

We report here the near full-length sequence characterization of 17 Danish clinical HIV-1 strains isolated from HLA-A02 patients not in need of ART, with relatively low viral loads and normal CD4 cell counts. Sequencing was performed directly on DNA extracted from short-term cocultures of PBMCs. The near full-length genomes did not contain any major insertions, deletions, or rearrangements. Sixteen of the isolates were characterized as nonrecombinant subtype B and one isolate as nonrecombinant subtype C. Phylogenetic analysis did not reveal any founder effect among the sequences. Also, we investigated the presence of infrequently targeted subdominant HLA-A02-binding CTL epitopes. The epitopes were conserved in the Danish strains as well as globally in reference sequences of all subtypes. Thus, the selected epitopes were not subtype-specific or region-specific. This lends support for the concept of a universal immunotherapeutic vaccine construct based on these epitopes.

Quality of life and depressive symptoms in patients with major depression and end-stage renal disease: a matched-pair study.

OBJECTIVE: To compare the quality of life (QOL) and depressive symptoms of outpatients with major depression with that of nondepressed individuals undergoing hemodialysis (matched for age, gender, and ethnicity). METHODS: We used the WHOQOL BREF and the Beck Depression Inventory (BDI). RESULTS: After univariate analyses, depressed patients' QOL scores were significantly lower (P<.0001) in all the assessed domains (i.e., physical health, psychological, social relationships, environmental, and global QOL). Additionally, there was a significant difference in the severity of depression among the study groups (P<.0001). Finally, after multiple regression analysis, the QOL profile of depressed subjects remained significantly worse even when controlling for depression scores and diagnostic status. CONCLUSION: The subjective QOL of patients with major depression is significantly lower than that of subjects undergoing hemodialysis.

Lesões não-cariosas na dentição decídua: relato de casos clínicos / Noncarious lesions in primary teeth: case reports

Este artigo relata três casos clínicos de erosão e atrição de dentes decíduos, em crianças na faixa etária entre 5 e 10 anos, atendidas na Clínica de Odontopediatria - UFSC. Após o diagnóstico clínico-radiográfico, o plano de tratamento variou para cada caso, utilizando-se de aplicação de fluoretos em diferentes concentrações, confecção de placa de proteção noturna, aconselhamento dietético e, principalmente, acompanhamento longitudinal com retornos mensais. É cada vez mais frequente a ocorrência de lesões não-cariosas em idades precoces que podem comprometer a unidade dente decíduo/germe do permanente e o sistema estomatognático como um todo. Portanto, o diagnóstico precoce e a instituição de um plano de tratamento adequado revestem-se de grande importância.

Psychache and suicidality in adult mood disordered outpatients in Brazil.

Shneidman (e.g., 1998) has theorized that psychache--general psychological and emotional pain that reaches intolerable intensity--is an important suicide-related variable, and indeed, represents a source of suicidal behavior. This conceptualization, while prominent and clinically and intuitively appealing, has received relatively little empirical scrutiny. In this study, we determined whether an index closely related to psychache, psychological quality of life, would display a special and resilient association to suicidality among 60 adult psychiatric outpatients in Brazil. All patients underwent structured clinical interviews and completed various clinical and quality-of-life measures. We found that the association between psychological quality of life and suicidality remained, even when depression, hopelessness, and other domains of quality of life were controlled. Psychache appears to deserve its place among key suicide-related variables, and deserves the attention of clinicians working with suicidal people.