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1.
J Clin Med ; 11(23)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36498779

RESUMO

BACKGROUND: Joint replacement surgeries have been known to be some of the most painful surgical procedures. Therefore, the options for postoperative pain management are of great importance for patients undergoing total knee arthroplasty (TKA). Despite successful surgery, up to 30% of the patients are not satisfied after the operation. The aim of this study is to assess pain development within the first 4 weeks after TKA in order to gain a better understanding and detect possible influencing factors. METHODS: A total of 103 patients were included in this prospective cohort study. Postoperative pain was indicated using a numeric rating scale (NRS). Furthermore, demographic data and perioperative parameters were correlated with the reported postoperative pain. RESULTS: The evaluation of postoperative pain scores showed a constant decrease in the first postoperative week (mean NRS score of 5.8 on day 1 to a mean NRS score of 4.6 on day 8). On day 9, the pain increased again. Thereafter, a continuous decrease in pain intensity from day 10 on was noted (continuous to a mean NRS score of 3.0 on day 29). A significant association was found between postoperative pain intensity and gender, body mass index (BMI), and preoperative leg axis. CONCLUSIONS: The increasing pain score after the first postoperative week is most likely due to more intensive mobilization and physiotherapy in the rehabilitation department. Patients that were female, had a low BMI, and a preoperative valgus leg axis showed a significantly higher postoperative pain scores. Pain management should consider these results in the future to improve patient satisfaction in the postoperative course after TKA.

2.
Contemp Sch Psychol ; 26(1): 22-33, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33500839

RESUMO

There is a nationwide shortage of school psychologists, and while NASP has recommended ways to increase recruitment and retention, the research on recruiting and retaining school psychologists, especially in high-need areas, is limited. Teacher education researchers have begun to address teacher shortages through "grow your own" training programs, but the research on these programs is also limited. A team of university school psychology faculty and regional education agency administrators developed a "Grow Your Own" school psychologist re-specialization training program to support recruiting and retaining school psychologists in rural areas. It is difficult for rural education agencies to recruit young professionals to their area, but it may be possible to recruit professionals currently living in the area to school graduate training programs. The partnership between the university school psychology training program and the regional education agencies addresses the school psychology shortage in one Midwestern state by recruiting special education and related educational professionals to school psychology. A focus of this program is to place more mental health professionals (i.e., school psychologists) in rural schools, therefore addressing the deficiency of mental health services in these rural areas. The partnership and the program are described, as are opportunities and challenges that the team has experienced to date.

4.
Orthopade ; 49(7): 635-646, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32542427

RESUMO

Idiopathic scoliosis is the largest group of all forms of scoliosis in the growth phase accounting for 80-90%. A distinction is made between idiopathic infantile (0-3 years), juvenile (4-10 years) and adolescent scoliosis (>10 years), depending on the age when scoliosis appears. The treatment depends on the skeletal age, the Cobb angle and the progression behavior of scoliosis. Mild cases are treated conservatively using physiotherapy, exercises and bracing but in advanced stages scoliosis should be surgically treated. With existing growth potential various techniques, such as traditional growing rods, magnetically controlled growth rods and vertebral body tethering are available. After the end of the growth phase a fusion should be recommended for scoliosis >50°.


Assuntos
Braquetes , Terapia por Exercício , Dispositivos de Fixação Ortopédica , Escoliose/terapia , Adolescente , Progressão da Doença , Humanos , Coluna Vertebral , Resultado do Tratamento
5.
Dev Psychopathol ; 32(3): 853-863, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31407649

RESUMO

Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.


Assuntos
Sistema Hipotálamo-Hipofisário , Receptores de Glucocorticoides , Metilação de DNA , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Leucócitos/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
6.
Am J Med Qual ; 35(4): 315-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31701768

RESUMO

Screening for depression is paramount to identify patients with depression and link them to care, yet only 29% of patients in the primary care center (PCC) were screened for depression in 2016. A baseline survey identified provider barriers to depression screening, including lack of time, support staff, and referral resources. The purpose of this project was to increase depression screening in the PCC using the Patient Health Questionnaire (PHQ-2/9). The authors created an educational program for staff and providers that included referral resources, treatment guidelines, and a decision-support tool in the electronic medical record. A retrospective chart review was performed, from January 2016 to June 2017, to determine the percentage of patients who received annual depression screening. During the program, the PCC saw an increase in depression screening rates. Thus, it is possible to overcome barriers to depression screening in a primary care setting by providing resources and education to clinicians.


Assuntos
Depressão/diagnóstico , Programas de Rastreamento/organização & administração , Atenção Primária à Saúde/organização & administração , População Urbana , Populações Vulneráveis , Centros Médicos Acadêmicos , Negro ou Afro-Americano , Atitude do Pessoal de Saúde , Doença Crônica , Comorbidade , Letramento em Saúde , Humanos , Encaminhamento e Consulta , Estudos Retrospectivos
7.
BMC Oral Health ; 19(1): 208, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488110

RESUMO

BACKGROUND: To evaluate early failure and possible risk factors for failure of dental implants placed under practice-based conditions. METHODS: To clarify the research question, anonymized data from 106 patients with 186 dental implants were analyzed. The presence of sucessful healing (yes/no) at the time of incorporation of the final prosthesis was assessed. Mixed models were compiled for each target variable to enable estimation of the effects of patient-related and implant-related conditions on the risk of early implant failure. RESULTS: Nine out of 186 implants (4.8%) placed in 106 participants failed before incorporation of the final prosthesis. The use of shorter implants (< 10 mm) and the need for augmentation procedures were associated with a greater risk of early implant failure. For shorter implants, the risk was 5.8 times greater than that for longer implants (p = 0.0230). Use of augmentation procedures increased the risk by a factor of 5.5 (p = 0.0174). CONCLUSIONS: Implants placed in the dental practice with a specialization in implantology heal successfully. The use of augmentation procedures and of implants shorter than 10 mm seems to be associated with a greater risk of early implant failure.


Assuntos
Implantação Dentária Endóssea/métodos , Implantes Dentários , Falha de Restauração Dentária , Carga Imediata em Implante Dentário , Adulto , Idoso , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osseointegração , Estudos Retrospectivos , Resultado do Tratamento
8.
Int J Oral Maxillofac Implants ; 34(5): 1169­1176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31107934

RESUMO

PURPOSE: The objective of this retrospective clinical study was to evaluate the short-term performance of implants and implant-supported dental restorations (single crowns, fixed/removable dental prostheses, and overdentures) and to identify risk factors for prosthetic complications under the conditions of general dental practice. MATERIALS AND METHODS: De-identified data extracted from electronic patient records were analyzed to clarify the research question. Patient-related variables and implant- and suprastructure-related variables were documented for each patient. The probability of complication-free survival after 1 and 2 years was evaluated using the Kaplan-Meier method. In addition, the prosthetic complications were analyzed using Cox regression models. RESULTS: Eighty-four patients with 134 healed dental implants supporting 107 restorations were studied over a clinical period of up to 52 months (mean: 23.9 months). Of the implants placed, nine (4.8%) failed during the healing phase. Of the healed implants, peri-implant bone loss occurred for two implants among two patients. Nonetheless, these two implants remained functional. Complications were as follows: peri-implantitis (1.5%), loss of retention (10%), loosening of the abutment screw (6%), and chipping of the veneer material (3.7%). The probability of complication-free survival for suprastructures alone was 92% (95% CI: 86% to 96%) after 1 year and 84% (95% CI: 75% to 90%) after 2 years of clinical service. Taking into consideration all complications/failures of implants and of restorations, complication-free survival was 86% (80% to 91%) and 79% (70% to 85%) after 1 and 2 years, respectively. CONCLUSION: Both healed dental implants and implant-supported restorations placed in general practice have a high incidence of success; the survival rates seen during the quite short observation period appear comparable to institutional study outcomes. However, technical prosthetic complications are not uncommon among general practice restorations and probably occur more often than in university studies.


Assuntos
Implantes Dentários , Peri-Implantite , Humanos , Estudos Retrospectivos
9.
Front Immunol ; 8: 1263, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29089944

RESUMO

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

10.
J Immunol ; 199(12): 4046-4055, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29133294

RESUMO

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69+CD8+ T cells (p = 0.022), increased numbers of HLA-DR+ CD4 and HLA-DR+ CD8 T cells (p < 0.001), as well as increased numbers of CD25+CD8+ T cells (p = 0.036). ELA also showed a trend toward higher numbers of CCR4+CXCR3-CCR6+ CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells.


Assuntos
Criança Adotada , Inflamação/etiologia , Acontecimentos que Mudam a Vida , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Estudos de Casos e Controles , Senescência Celular , Criança Institucionalizada , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Síndromes de Imunodeficiência/etiologia , Síndromes de Imunodeficiência/imunologia , Imunofenotipagem , Inflamação/imunologia , Interleucina-6/sangue , Luxemburgo , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Obesidade/epidemiologia , Fumar/epidemiologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/imunologia , Homeostase do Telômero/imunologia , Adulto Jovem
11.
Artif Organs ; 41(2): 122-129, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27582339

RESUMO

At our institute a total artificial heart is being developed. It is directly actuated by a linear drive in between two ventricles, which comprise membranes to separate the drive and blood flow. A compliance chamber (CC) is needed to reduce pressure peaks in the ventricles and to increase the pump capacity. Therefore, the movement of the membrane is supported by applying a negative pressure to the air volume inside the drive unit. This study presents the development of the implantable CC which is connected to the drive unit of the total artificial hearts (TAH). The anatomical fit of the CC is optimized by analyzing CT data and adapting the outer shape to ensure a proper fit. The pressure peaks are reduced by the additional volume and the flexible membrane of the CC. The validation measurements of change in pressure peaks and flow are performed using the complete TAH system connected to a custom mock circulation loop. Using the CC, the pressure peaks could be damped below 5 mm Hg in the operational range. The flow output was increased by up to 14.8% on the systemic side and 18.2% on the pulmonary side. The described implantable device can be used for upcoming chronic animal trials.


Assuntos
Coração Artificial , Coração/anatomia & histologia , Hemodinâmica , Humanos , Desenho de Prótese , Implantação de Prótese , Tórax/anatomia & histologia
12.
Nucleic Acids Res ; 44(6): 2628-45, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-26615195

RESUMO

The variability and complexity of the transcription initiation process was examined by adapting RNA ligase-mediated rapid amplification of 5' cDNA ends (5'-RACE) to Next-Generation Sequencing (NGS). We oligo-labelled 5'-m(7)G-capped mRNA from two genes, the simple mono-exonic Beta-2-Adrenoceptor (ADRB2R)and the complex multi-exonic Glucocorticoid Receptor (GR, NR3C1), and detected a variability in TSS location that has received little attention up to now. Transcription was not initiated at a fixed TSS, but from loci of 4 to 10 adjacent nucleotides. Individual TSSs had frequencies from <0.001% to 38.5% of the total gene-specific 5' m(7)G-capped transcripts. ADRB2R used a single locus consisting of 4 adjacent TSSs. Unstimulated, the GR used a total of 358 TSSs distributed throughout 38 loci, that were principally in the 5' UTRs and were spliced using established donor and acceptor sites. Complete demethylation of the epigenetically sensitive GR promoter with 5-azacytidine induced one new locus and 127 TSSs, 12 of which were unique. We induced GR transcription with dexamethasone and Interferon-γ, adding one new locus and 185 additional TSSs distributed throughout the promoter region. In-vitro the TSS microvariability regulated mRNA translation efficiency and the relative abundance of the different GRN-terminal protein isoform levels.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Técnicas de Amplificação de Ácido Nucleico , Receptores Adrenérgicos beta 2/genética , Receptores de Glucocorticoides/genética , Sítio de Iniciação de Transcrição , Iniciação da Transcrição Genética , Regiões 5' não Traduzidas , Azacitidina/farmacologia , Linhagem Celular Tumoral , Dexametasona/farmacologia , Éxons , Loci Gênicos , Variação Genética , Humanos , Interferon gama/farmacologia , Íntrons , Oligonucleotídeos/química , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Capuzes de RNA/genética , Capuzes de RNA/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Glucocorticoides/metabolismo , Coloração e Rotulagem , Iniciação da Transcrição Genética/efeitos dos fármacos
13.
Biochim Biophys Acta ; 1839(11): 1051-61, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25150144

RESUMO

GR transcripts display a remarkable heterogeneity in their 5' untranslated regions (5'UTRs). These variable 5'UTRs are encoded by a series of alternative 1st exons, and together with their associated promoters they maintain tissue-specific GR expression levels. In this study we over-expressed GR transcripts containing individual 1st exons, and assessed their effect on RNA stability, 3'-splicing, translation initiation and protein isoform production. We showed that these alternative 5'UTRs influence the predicted mRNA structure and free energy, and were associated with differential levels of functional spliced mRNA. However, the 5'UTR had little influence on the relative levels of the two principal 3' splice transcripts, GR-α and -ß. The overall mRNA length, the free energy of the transcript and the translational efficiency directly influenced total GR levels. However, individual N-terminal protein isoform levels appeared to depend upon elements within the 5'UTR. Membrane-GR specific labelling suggested that the mGR originates from transcripts containing exon 1D and possibly 1H, although the specific trafficking sequences or structures within these transcripts remain unidentified. The role of the alternative first exons and their associated 5'UTRs has now been expanded to translational control, influencing total GR levels, individual constituent isoform levels, as well as trafficking to the cell surface.


Assuntos
Regiões 5' não Traduzidas , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Processamento Alternativo , Meia-Vida , Humanos , Conformação de Ácido Nucleico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transporte Proteico , Processamento Pós-Transcricional do RNA/genética , Estabilidade de RNA , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Células Tumorais Cultivadas
14.
J Proteomics ; 108: 325-36, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24914991

RESUMO

Quantitative gel-based proteomics (2D DIGE coupled to MALDI-TOF/TOF MS) has been used to investigate the effects of different measles virus (MV) strains on the host cell proteome. A549/hSLAM cells were infected either with wild type MV strains, an attenuated vaccine or a multiple passaged Vero cell adapted strain. By including interferon beta treatment as a control it was possible to distinguish between the classical antiviral response and changes induced specifically by the different strains. Of 38 differentially expressed proteins in total (p-value ≤0.05, fold change ≥2), 18 proteins were uniquely modulated following MV infection with up to 9 proteins specific per individual strain. Interestingly, wt strains displayed distinct protein patterns particularly during the late phase of infection. Proteins were grouped into cytoskeleton, metabolism, transcription/translation, immune response and mitochondrial proteins. Bioinformatics analysis revealed mostly changes in proteins regulating cell death and apoptosis. Surprisingly, wt strains affected the cytokeratin system much stronger than the vaccine strain. To our knowledge, this is the first study on the MV-host proteome addressing interstrain differences. BIOLOGICAL SIGNIFICANCE: In the present study we investigated the host cell proteome upon measles virus (MV) infection. The novelty about this study is the side-by side comparison of different strains from the same virus, which has not been done at the proteome level for any other virus including MV. We used different virus strains including a vaccine strain, wild type isolates derived from MV-infected patients as well as a Vero cell adapted strain, which serves as an intermediate between vaccine and wild type strain. We observed differences between vaccine and wild type strains as well as common features between different wild type strains. Perhaps one of the most surprising findings was that differences did not only occur between wild type and vaccine or Vero cell adapted strains but also between different wild type strains. In fact our study suggests that besides the cytokeratin and the IFN system wild type viruses seem to differ as much among each other than from vaccine strains. Thus our results are suggestive of complex and diverse virus-host interactions which differ considerably between different wild type strains. Our data indicate that interstrain differences are prominent and have so far been neglected by proteomics studies.


Assuntos
Interações Hospedeiro-Patógeno , Vírus do Sarampo/fisiologia , Sarampo/metabolismo , Proteoma/metabolismo , Proteômica , Proteínas Virais/metabolismo , Animais , Células CHO , Chlorocebus aethiops , Cricetinae , Cricetulus , Citoesqueleto/imunologia , Citoesqueleto/metabolismo , Humanos , Sarampo/imunologia , Proteínas Mitocondriais/imunologia , Proteínas Mitocondriais/metabolismo , Biossíntese de Proteínas/imunologia , Proteoma/imunologia , Especificidade da Espécie , Transcrição Gênica/imunologia , Células Vero , Proteínas Virais/imunologia
15.
Mol Cell Proteomics ; 12(7): 1764-79, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23339905

RESUMO

Glucocorticoids exert rapid nongenomic effects by several mechanisms including the activation of a membrane-bound glucocorticoid receptor (mGR). Here, we report the first proteomic study on the effects of mGR activation by BSA-conjugated cortisol (Cort-BSA). A subset of target proteins in the proteomic data set was validated by Western blot and we found them responding to mGR activation by BSA-conjugated cortisol in three additional cell lines, indicating a conserved effect in cells originating from different tissues. Changes in the proteome of BSA-conjugated cortisol treated CCRF-CEM leukemia cells were associated with early and rapid pro-apoptotic, immune-modulatory and metabolic effects aligning with and possibly "priming" classical activities of the cytosolic glucocorticoid receptor (cGR). PCR arrays investigating target genes of the major signaling pathways indicated that the mGR does not exert its effects through the transcriptional activity of any of the most common kinases in these leukemic cells, but RhoA signaling emerged from our pathway analysis. All cell lines tested displayed very low levels of mGR on their surface. Highly sensitive and specific in situ proximity ligation assay visualized low numbers of mGR even in cells previously thought to be mGR negative. We obtained similar results when using three distinct anti-GR monoclonal antibodies directed against the N-terminal half of the cGR. This strongly suggests that the mGR and the cGR have a high sequence homology and most probably originate from the same gene. Furthermore, the mGR appears to reside in caveolae and its association with caveolin-1 (Cav-1) was clearly detected in two of the four cell lines investigated using double recognition proximity ligation assay. Our results indicate however that Cav-1 is not necessary for membrane localization of the GR since CCRF-CEM and Jurkat cells have a functional mGR, but did not express this caveolar protein. However, if expressed, this membrane protein dimerizes with the mGR modulating its function.


Assuntos
Hidrocortisona/farmacologia , Receptores de Glucocorticoides/metabolismo , Soroalbumina Bovina/farmacologia , Caveolina 1 , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Glucocorticoides , Humanos , Células Jurkat , Células MCF-7 , Proteômica
16.
PLoS One ; 6(7): e22389, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21811596

RESUMO

UNLABELLED: Lantibiotics are small peptide antibiotics that contain the characteristic thioether amino acids lanthionine and methyllanthionine. As ribosomally synthesized peptides, lantibiotics possess biosynthetic gene clusters which contain the structural gene (lanA) as well as the other genes which are involved in lantibiotic modification (lanM, lanB, lanC, lanP), regulation (lanR, lanK), export (lanT(P)) and immunity (lanEFG). The lantibiotic mersacidin is produced by Bacillus sp. HIL Y-85,54728, which is not naturally competent. METHODOLOGY/PRINCIPAL FINDINGS: The aim of these studies was to test if the production of mersacidin could be transferred to a naturally competent Bacillus strain employing genomic DNA of the producer strain. Bacillus amyloliquefaciens FZB42 was chosen for these experiments because it already harbors the mersacidin immunity genes. After transfer of the biosynthetic part of the gene cluster by competence transformation, production of active mersacidin was obtained from a plasmid in trans. Furthermore, comparison of several DNA sequences and biochemical testing of B. amyloliquefaciens FZB42 and B. sp. HIL Y-85,54728 showed that the producer strain of mersacidin is a member of the species B. amyloliquefaciens. CONCLUSIONS/SIGNIFICANCE: The lantibiotic mersacidin can be produced in B. amyloliquefaciens FZB42, which is closely related to the wild type producer strain of mersacidin. The new mersacidin producer strain enables us to use the full potential of the biosynthetic gene cluster for genetic manipulation and downstream modification approaches.


Assuntos
Bacillus/metabolismo , Bacteriocinas/metabolismo , Peptídeos/metabolismo , Bacillus/enzimologia , Bacillus/genética , Bacillus/imunologia , Bacteriocinas/biossíntese , Bacteriocinas/química , Bacteriocinas/isolamento & purificação , Sequência de Bases , DNA Girase/genética , Dados de Sequência Molecular , Família Multigênica/genética , Peptídeos/química , Peptídeos/isolamento & purificação , Filogenia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
17.
Clin Gastroenterol Hepatol ; 8(10): 870-6, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20670694

RESUMO

BACKGROUND & AIMS: Screening recommendations for colorectal cancer (CRC) commonly take family history but no other risk factors into account. We compared and assessed risk factors of colorectal polyps in a large population undergoing screening colonoscopy. METHODS: We conducted a population-based cross-sectional study that included 3349 subjects, 55 years or older (mean ages of men and women, 63.6 and 63.4 years, respectively), who underwent colonoscopy for the first time within the nationwide colonoscopy screening program in Germany. We calculated prevalences of colorectal polyps and estimated multivariate prevalence ratios (PRs) and population attributable fractions (PAFs). RESULTS: Overall, 654 subjects had hyperplastic polyps (20%), 675 had non-advanced adenomas (20%), 343 had advanced adenomas (10%), and 40 had CRC (1%). Risk factor prevalences and adjusted PRs were higher for male gender and smoking than for family history of CRC. PAFs for prevalence of non-advanced and advanced neoplasia were highest for male gender (23% and 23%, respectively), followed by smoking (7% and 9%, respectively), and family history of CRC (2% and 4%, respectively). CONCLUSIONS: Male gender and smoking have a larger impact on the prevalence of colorectal neoplasia than family history, suggesting an extensive evaluation of additional risk stratification in population-based screening, particularly by sex.


Assuntos
Adenoma/epidemiologia , Pólipos do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Saúde da Família , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos
18.
Horm Behav ; 56(1): 140-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19361511

RESUMO

Social behavior changes dramatically during primate adolescence. However, the extent to which testosterone and other gonadal hormones are necessary for adolescent social behavioral development is unknown. In this study, we determined that gonadectomy significantly impairs social dominance in naturalistic settings and changes reactions to social stimuli in experimental settings. Rhesus macaques were castrated (n= 6) or sham operated (n=6) at age 2.4 years, group-housed for 2 years, and ethograms were collected weekly. During adolescence the gonadally intact monkeys displayed a decrease in subordinate behaviors and an increase in dominant behaviors, which ultimately related to a rise in social status and rank in the dominance hierarchy. We measured monkey's reactions to emotional faces (fear, threat, neutral) of conspecifics of three ages (adult, peer, infant). Intact monkeys were faster to retrieve a treat in front of a threatening or infant face, while castrated monkeys did not show a differential response to different emotional faces or ages. No group difference in reaction to an innate fear-eliciting object (snake) was found. Approach and proximity responses to familiar vs unfamiliar conspecifics were tested, and intact monkeys spent more time proximal to a novel conspecific as compared to castrates who tended to spend more time with a familiar conspecific. No group differences in time spent with novel or familiar objects were found. Thus, gonadectomy resulted in the emergence of significantly different responses to social stimuli, but not non-social stimuli. Our work suggests that intact gonads, which are needed to produce adolescent increases in circulating testosterone, impact social behavior during adolescences in primates.


Assuntos
Envelhecimento/psicologia , Orquiectomia/psicologia , Comportamento Social , Análise de Variância , Animais , Peso Corporal/fisiologia , Ritmo Circadiano , Emoções , Estradiol/sangue , Comportamento Exploratório/fisiologia , Expressão Facial , Hormônio Luteinizante/sangue , Macaca mulatta , Masculino , Mães , Radioimunoensaio , Predomínio Social , Percepção Social , Testosterona/sangue , Fatores de Tempo
19.
Twin Res Hum Genet ; 10(1): 33-44, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17539363

RESUMO

There is significant covariation between internalizing and externalizing behavior, although there is also evidence that internalizing behavior is a protective factor against externalizing behavior. Several researchers have posited that the examination of the relationship between temperament or personality and behavior problems may help explain these seemingly contradictory results. Specifically, negative emotionality or neuroticism has been cited as a temperament characteristic that internalizing and externalizing behavior share in common, whereas behavioral inhibition may be related only to internalizing behavior. We examined the degree to which the covariation between internalizing and externalizing behavior assessed from age 4 to 12 years can be explained by temperament characteristics assessed from age 14 to 36 months. Additionally, we assessed the extent to which this relationship is due to genetic or environmental factors, analyzing data from 225 monozygotic and 185 dizygotic twin pairs assessed by the Colorado Longitudinal Twin Study. In males, a portion of the covariation between internalizing and externalizing behavior was explained by shared environmental influences in common with emotionality and shared environmental influences in common with shyness. In females, most of the covariation between internalizing and externalizing behavior was explained by shared environmental influences in common with emotionality. A possible limitation of this study is that the covariation between temperament and behavior problems may be due to shared measurement variance, as parent ratings were used to assess both temperament and behavior problems.


Assuntos
Transtornos do Comportamento Infantil , Emoções , Inibição Psicológica , Temperamento , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Análise de Variância , Criança , Transtornos do Comportamento Infantil/epidemiologia , Transtornos do Comportamento Infantil/genética , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Colorado , Meio Ambiente , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Variações Dependentes do Observador , Relações Pais-Filho , Fatores Sexuais , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologia
20.
Appl Environ Microbiol ; 72(11): 7270-7, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16980420

RESUMO

The lantibiotic (lanthionine-containing antibiotic) mersacidin is an antimicrobial peptide consisting of 20 amino acids and is produced by Bacillus sp. strain HIL Y-85,54728. The structural gene (mrsA) and the genes for producer self-protection, modification enzymes, transport proteins, and regulator proteins are organized in a 12.3-kb biosynthetic gene cluster on the chromosome of the producer strain. Mersacidin is produced in stationary phase in a synthetic medium (K. Altena, A. Guder, C. Cramer, and G. Bierbaum, Appl. Environ. Microbiol. 66:2565-2571, 2000). To investigate the influence of the alternative sigma factor H on mersacidin biosynthesis, a SigH knockout was constructed. The knockout mutant was asporogenous, and a comparison to the wild-type strain indicated no significant differences concerning mersacidin production and immunity. Characterization of the mrsA promoter showed that the gene is transcribed by the housekeeping sigma factor A. The biosynthesis of some lantibiotic peptides like nisin or subtilin is regulated in a cell-density-dependent manner (M. Kleerebezem, Peptides 25:1405-1414, 2004). When mersacidin was added at a concentration of 2 mg/liter to an exponentially growing culture, an earlier production of antibacterial activity against Micrococcus luteus ATCC 4698 in comparison to that of the control culture was observed, suggesting that mersacidin itself functions as an autoinducer. In real-time PCR experiments, the expression of mrsA was remarkably increased in the induced culture compared to the control. In conclusion, mersacidin is yet another lantibiotic peptide whose biosynthesis can be regulated by an autoinducing mechanism.


Assuntos
Antibacterianos/biossíntese , Bacillus/metabolismo , Bacteriocinas/biossíntese , Regulação Bacteriana da Expressão Gênica , Família Multigênica , Peptídeos/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus/genética , Bacillus/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteriocinas/química , Bacteriocinas/farmacologia , Sequência de Bases , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/farmacologia , Análise de Sequência de DNA , Fator sigma/genética , Fator sigma/metabolismo
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