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1.
Ann Oncol ; 35(8): 728-738, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38866180

RESUMO

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Neoplasias do Endométrio , Paclitaxel , Humanos , Feminino , Carboplatina/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Método Duplo-Cego , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão , Anticorpos Monoclonais Humanizados
2.
Eur Spine J ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811437

RESUMO

PURPOSE: Surgical stabilization of the spine by vertebral body replacement (VBR) is used for spinal disorders such as traumatic fractures to provide an anatomical re-adjustment of the spine to prevent late detrimental effects and pain [1-4]. This study addresses the clinical outcome after a ventral intervention with VBR and bisegmental fusion. METHODS: The study includes 76 patients (mean age: 59.34 ± 15.97; 34 females and 42 males) with fractures in the lower thoracic and lumbar spine. They were selected from patients of our hospital who received an anterolateral VBR surgery on the corresponding lower spine region over a nine-year period. Only patients were examined with X-rays and complete follow-up records. Exclusion criteria were changes due to degeneration and pathological fractures. Patients were divided into two groups, the thoracotomy group (Th10-L1) and the lumbotomy group (L2-5), respectively. Minimum one year after surgery, patients were asked about their well-being using a precasted questionnaire. RESULTS: No significant differences with respect to the subjective impression of the patients concerning their back pain, spinal functional impairment, their general functional status and their quality of life impairment. Unfortunately, however, only a rather modest but significant increase of the post-surgical life quality was reported. CONCLUSIONS: Patients who underwent VBR in the lower thoracic or lumbar spine show modest long-term well-being. The results suggest that injuries to the lower thoracic or lumbar spine requiring vertebral body replacement should be classified as severe injuries since they adversely affect the patients' long-term well-being. TRIAL REGISTRATION: Study of clinical outcome of patients after vertebral body replacement of the ventral thoracal and lumbal spine, DRKS00031452. Registered 10th March 2023 - Prospectively registered. Trial registration number DRKS00031452.

3.
J Environ Manage ; 370: 122795, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39383740

RESUMO

Micropollutants (MPs) encompass a range of human-made pollutants present in trace amounts in environmental systems. MPs include pharmaceuticals, personal care products, pesticides, persistent organic pollutants, micro- and nano-plastics, and artificial sweeteners, all posing ecological risks. Conventional municipal wastewater treatment methods often face challenges in completely removing MPs due to their chemical characteristics, stability, and resistance to biodegradation. In this research, an Advanced Oxidation Process, combining hydrodynamic cavitation (HC) with dissolved ozone (O3) and side injection, was employed to efficiently degrade succinic acid (SA), an ozone-resistant compound and common byproduct. The HC/O3 process was run to treat different synthetic effluents, focusing on evaluating the influence of O3-to-total organic carbon (TOC) ratio, cavitation number (Cv) and O3 dosage. Notably, the results from a series of 14 experiments highlighted the critical significance of a low O3-to-TOC ratio value of 0.08 mg/mg and Cv value of 0.056 in HC for achieving efficient SA removal of 41.2% from an initial SA solution (106.3 mg/L). Regarding a series of four proof-of-concept experiments and their replications, the average TOC removal reached 62% when treating wastewater treatment plant effluent spiked with SA. This significant removal rate was achieved under initial conditions: Cv of 0.02, O3-to-TOC ratio set at 0.77 mg/mg, TOC concentration of 47.7 mg/L, 106 mg/L of SA, and a temperature of 25 °C. Notably, the electrical energy per order required for the 62% reduction in TOC was a modest 12.5 kWh/m3/order, indicating the potential of the continuous HC/O3 process as a promising approach for degrading a wide range of MPs.

4.
Arch Orthop Trauma Surg ; 144(7): 2955-2965, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38847834

RESUMO

INTRODUCION: The malimplantation of the total knee arthroplasty (TKA) components is one of the main reasons for revision surgery. For determining the correct intraoperative femoral rotation several anatomic rotational axes were described in order to achieve a parallel, balanced flexion gap. In this cadaveric study prevalent used rotational femoral axes and a navigated functional rotational axis were compared to the flexion-extension axis defined as the gold standard in rotation for femoral TKA component rotation. MATERIALS AND METHODS: Thirteen body donors with knee osteoarthritis (mean age: 78.85 ± 6.09; eight females and five males) were examined. Rotational computer tomography was performed on their lower extremities pre- and postoperatively. Knee joint arthroplasties were implanted and CT diagnostics were used to compare the preoperatively determined flexion-extension axis (FEA). The FEA is the axis determined by our surgical technique and serves as an internal reference. It was compared to other axes such as (i) the anatomical transepicondylar axis (aTEA), (ii) the surgical transepicondylar axis (sTEA), (iii) the posterior condylar axis (PCA) and (iv) the functional rotation axis (fRA). RESULTS: Examination of 26 knee joint arthroplasties revealed a significant angular deviation (p*** < 0.0001) for all axes when the individual axes and FEA were compared. aTEA show mean angular deviation of 5.2° (± 4.5), sTEA was 2.7° (± 2.2), PCA 2.9° (± 2.3) and the deviation of fRA was 4.3° (± 2.7). A tendency towards external rotation was observed for the relative and maximum axis deviations of the aTEA to the FEA, for the sTEA and the fRA. However, the rotation of the posterior condylar axis was towards inwards. CONCLUSIONS: All axes showed a significant angular deviation from the FEA. We conclude that the presented technique achieves comparable results in terms of FEA reconstruction when compared with the use of the known surrogate axes, with certain deviations in terms of outliers in the internal or external rotation.


Assuntos
Artroplastia do Joelho , Cadáver , Fêmur , Humanos , Artroplastia do Joelho/métodos , Feminino , Masculino , Idoso , Rotação , Fêmur/cirurgia , Fêmur/diagnóstico por imagem , Idoso de 80 Anos ou mais , Tomografia Computadorizada por Raios X , Amplitude de Movimento Articular , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/diagnóstico por imagem , Prótese do Joelho , Articulação do Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem
5.
Philos Trans A Math Phys Eng Sci ; 381(2243): 20220139, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36709772

RESUMO

The stability of a non-isothermal circular Couette flow is analyzed when subjected to a dielectrophoretic force field. Outward and inward heating configurations are considered when the inner cylinder is rotating and the outer cylinder is at rest. In addition, an alternating voltage is applied between the two cylinders to induce a radial electric buoyancy that acts on the dielectric fluid. The linear stability analysis provides the threshold for the first transition to instability, as well as the corresponding wavenumber and frequency of the modes. This article is part of the theme issue 'Taylor-Couette and related flows on the centennial of Taylor's seminal Philosophical Transactions paper (part 1)'.

6.
Radiologe ; 62(3): 271-284, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-35238995

RESUMO

Instability and impingement of the hip are the main pathomechanisms that can lead to chondrolabral damage, painful restriction of motion and early hip osteoarthritis due to increased mechanical stress, even in young patients. The goals of joint-preserving hip surgery are correction of the osseous deformities and chondrolabral damage as well as restoration of joint function. A prerequisite for successful surgery is the identification of the underlying hip pathologies, which can also occur in combination. Dedicated radiographic and magnetic resonance (MR) imaging of osseous morphology and the internal degenerative joint lesions play an essential role for the treatment indications and surgical treatment planning. This article provides a concise overview of the prevalence, pathomechanisms and indicated treatment of hip deformities as well as detailed recommendations on the specific radiological clarification.


Assuntos
Impacto Femoroacetabular , Osteoartrite do Quadril , Artroscopia/métodos , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/cirurgia
7.
Calcif Tissue Int ; 108(3): 346-353, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33226445

RESUMO

Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including GNAS-mutation analysis from patients' medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5-48.9), cervical cancer (4.93, 95%CI 1.7-8.2), thyroid cancer (3.71, 95% CI 1.1-7.8), prostate cancer (3.08, 95% CI 1.8-4.6), and melanoma (2.01, 95%CI 1.2-3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated.


Assuntos
Displasia Fibrosa Poliostótica , Neoplasias , Displasia Fibrosa Poliostótica/epidemiologia , Humanos , Neoplasias/epidemiologia , Países Baixos , Prevalência , Sistema de Registros
8.
Philos Trans A Math Phys Eng Sci ; 378(2176): 20190267, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32623988

RESUMO

Seeking a sustainable and selective approach for terpene modification, a catalyst deconvolution approach was applied to the Meinwald rearrangement of (+)-limonene oxide as a model substrate to yield dihydrocarvone. In order to identify the most suitable catalyst and reaction conditions, different Lewis acids were evaluated. Bismuth triflate proved to be the most active catalyst under mild reaction conditions, with a low catalyst loading (1 mol%) and a relatively short reaction time (3 h). The optimized reaction conditions were subsequently transferred to other terpene-based epoxides, yielding different bio-based biscarbonyl structures, which constitute interesting and valuable substances, e.g. for polymer synthesis or as fragrances. Monoepoxides derived from (R)-(-)-carvone and (+)-dihydrocarvone rearranged to the desired products with high selectivities and yields. γ-Terpinene dioxide could be transformed in a double rearrangement to the respective biscarbonyl in moderate yields. A better result was achieved for limonene dioxide after further adjustment of the protocol to reach acceptable yields with a low catalyst loading of 0.1 mol% using 2-methyl tetrahydrofuran as a sustainable solvent. Compared to many procedures described in the literature, this procedure represents a step towards an increased sustainability in terpene modification by considering several principles of Green Chemistry, such as renewable resources, catalysis and mild reaction conditions for elementary chemical transformations. This article is part of a discussion meeting issue 'Science to enable the circular economy'.

9.
J Chem Phys ; 152(5): 051102, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32035470

RESUMO

In this work, the adsorption height of Ag adatoms on the Fe3O4(001) surface after exposure to CO was determined using normal incidence x-ray standing waves. The Ag adatoms bound to CO (Ag1 CO) are found to be pulled out of the surface to an adsorption height of 1.15 Å ± 0.08 Å, compared to the previously measured height of 0.96 Å ± 0.03 Å for bare Ag adatoms and clusters. Utilizing DFT+vdW+U calculations with the substrate unit cell dimension fixed to the experimental value, the predicted adsorption height for Ag1 CO was 1.16 Å, in remarkably good agreement with the experimental results.

10.
World J Urol ; 36(7): 1085-1091, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29497859

RESUMO

PURPOSE: To establish whether bipolar transurethral resection of tumours (bTURB) on the lateral bladder wall is superior to monopolar transurethral resection (mTURB) of such tumours. To our knowledge, this is the first prospective randomised study, which defines complete resection depending on obturator jerk as primary endpoint. METHODS: In a prospective, randomised, single centre study, 52 patients with newly diagnosed or recurrent bladder tumour on the lateral bladder wall were enrolled and randomised to undergo mTURB or bTURB; 44 patients were eligible for analysis, of whom 21 underwent mTURB and 23 bTURB. Any differences between the two techniques related to the incidence of unwanted stimulation of the obturator nerve and subsequent adductor spasms were evaluated. All procedures were carried out under laryngeal mask anaesthesia without obturator nerve block (ONB) and without drug-induced relaxation. RESULTS: Baseline characteristics of the two study groups did not differ statistically significantly. The success rate defined as complete resection of the bladder tumour without any clinically relevant adductor spasm was 61.9% in the monopolar group and 82.6% in the bipolar group (p = 0.18). CONCLUSIONS: Complete, undisturbed resection of tumours of the lateral bladder wall is feasible with mTURB and bTURB. Adductor spasms due to obturator jerk can occur suddenly with the risk of bladder perforation. We therefore support ONB when using spinal anaesthesia and drug-induced relaxation when using general anaesthesia when performing TURB on the lateral bladder wall.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Bloqueio Nervoso , Nervo Obturador , Espasmo/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Carga Tumoral , Neoplasias da Bexiga Urinária/patologia
11.
Phys Chem Chem Phys ; 20(24): 16469-16476, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29882949

RESUMO

The normal incidence X-ray standing wave (NIXSW) technique has been used to follow the evolution of the adsorption geometry of Ni adatoms on the Fe3O4(001)-(√2 × âˆš2)R45° surface as a function of temperature. Two primary surface region sites are identified: a bulk-continuation tetrahedral site and a sub-surface octahedral site, the latter site being preferred at higher annealing temperatures. The ease of incorporation is linked to the presence of subsurface cation vacancies in the (√2 × âˆš2)R45° reconstruction and is consistent with the preference for octahedral coordination observed in the spinel compound NiFe2O4.

12.
J Viral Hepat ; 24(8): 662-671, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28182305

RESUMO

Current treatment options for patients with chronic hepatitis B virus (HBV) infection are not curative as they are not effective in eliminating covalently closed circular DNA (cccDNA). cccDNA is a stable template for HBV transcription in the nucleus of hepatocytes and is thought to be one of the main factors responsible for HBV persistence. Recently, activation of the lymphotoxin beta receptor (LTßR) has been shown to trigger degradation of cccDNA through induction of cytidine deaminases of the APOBEC3 family in HBV cell culture model systems. To assess the presence and relevance of such mechanisms in the liver of chronically HBV-infected patients, we compared intrahepatic cccDNA levels with the expression levels of lymphotoxins and some of their target genes (eg APOBEC deaminases) in liver biopsy tissue. Our results confirm elevated gene expression levels of components of the lymphotoxin pathway including lymphotoxin alpha (LTα), lymphotoxin beta (LTß), APOBEC3B (A3B) and APOBEC3G (A3G) in the chronically HBV-infected liver compared to uninfected liver. Furthermore, expression levels of the genes of the APOBEC deaminase family were correlated with those of LTα and LTß gene expression, consistent with lymphotoxin-mediated upregulation of APOBEC gene expression. However, intrahepatic cccDNA and HBV replication levels were not correlated with LTα, LTß and APOBEC gene expression. In conclusion, these results suggest that although the lymphotoxin pathway is activated in the chronically HBV-infected liver, it has no major impact on HBV cccDNA metabolism in chronic HBV infection.


Assuntos
DNA Circular/análise , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Homeostase , Receptor beta de Linfotoxina/metabolismo , Linfotoxina-alfa/metabolismo , Citidina Desaminase/metabolismo , Perfilação da Expressão Gênica , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Humanos
13.
Eur J Vasc Endovasc Surg ; 53(2): 262-267, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27876561

RESUMO

OBJECTIVE/BACKGROUND: Central venous tunnelled hemodialysis catheters (CVTC) are used for initial vascular access in patients with renal failure. Tip design of the CVTC may play an important role in catheter function and complication rates, influencing adequate hemodialysis treatment of these patients. METHODS: This prospective, observational cohort study compared the function and complication rates of two CVTCs in patients with end stage renal disease (ESRD) within a follow-up period of 24 months. The study included patients with ESRD who received either a CVTC with a split tip (ST) or a shotgun tip (SG). All patients underwent dialysis within 24 h of intervention. Blood flow was documented initially (Qb0) and was followed up after 6 (Qb6), 12 (Qb12), and 24 (Qb24) months. Analysis of blood flow and complication rates within the follow-up period was performed by questionnaires. RESULTS: In total, 185 patients were included, of whom 93 received a ST CVTC and 92 a SG CVTC. Baseline parameters did not differ significantly between groups. CVTC blood flow was not significantly different between the two devices. Thrombolytic therapy with Alteplase was used significantly more often in the ST group (29%) than in the SG group (16%) (p < 0.05). The CVTC replacement rate was significantly higher in the ST group (19.3%) compared with the SG group (8.7%) (p < 0.05). CONCLUSIONS: The tip design of CVTC (split or shotgun) appears to be irrelevant for long-term blood flow during dialysis treatment. However, patients may benefit from SG catheters over ST catheters where replacement rates and thrombolytic treatment are concerned.


Assuntos
Obstrução do Cateter/etiologia , Cateterismo Venoso Central/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Remoção de Dispositivo , Falência Renal Crônica/terapia , Diálise Renal , Trombose/etiologia , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Cateterismo Venoso Central/efeitos adversos , Desenho de Equipamento , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fluxo Sanguíneo Regional , Fatores de Risco , Inquéritos e Questionários , Terapia Trombolítica , Trombose/diagnóstico , Trombose/fisiopatologia , Trombose/terapia , Fatores de Tempo , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
14.
Psychol Med ; 46(4): 877-89, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26620720

RESUMO

BACKGROUND: To our knowledge, there are no universal screening tools for substance dependence that (1) were developed using a population-based sample, (2) estimate total risk briefly and inexpensively by incorporating a relatively small number of well-established risk factors, and (3) aggregate risk factors using a simple algorithm. We created a universal screening tool that incorporates these features to identify adolescents at risk for persistent substance dependence in adulthood. METHOD: Participants were members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972-1973 and followed prospectively to age 38 years, with 95% retention. We assessed a small set of childhood and adolescent risk factors: family history of substance dependence, childhood psychopathology (conduct disorder, depression), early exposure to substances, frequent substance use in adolescence, sex, and childhood socioeconomic status. We defined the outcome (persistent substance dependence in adulthood) as dependence on one or more of alcohol, tobacco, cannabis, or hard drugs at ⩾3 assessment ages: 21, 26, 32, and 38 years. RESULTS: A cumulative risk index, a simple sum of nine childhood and adolescent risk factors, predicted persistent substance dependence in adulthood with considerable accuracy (AUC = 0.80). CONCLUSIONS: A cumulative risk score can accurately predict which adolescents in the general population will develop persistent substance dependence in adulthood.


Assuntos
Comportamento do Adolescente , Transtorno da Conduta/epidemiologia , Depressão/epidemiologia , Classe Social , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Tabagismo/epidemiologia , Adolescente , Adulto , Alcoolismo/epidemiologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Abuso de Maconha/epidemiologia , Nova Zelândia/epidemiologia , Estudos Prospectivos , Medição de Risco , Adulto Jovem
15.
Klin Padiatr ; 228(1): 11-6, 2016 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-26766668

RESUMO

BACKGROUND: Based on an increasing number of outpatient treatments, an extensive demand planning is necessary to ensure the quality of medical care. University outpatient clinics are special parts of this sector and therefore it is necessary that a research demonstrates the nearly uninvestigated position of a paediatric outpatient clinic. PATIENTS: The research at the university hospital for children and adolescents in Leipzig started in 2009 to survey 2283 of in total 9391 patients and the physicians. METHODS: Sociodemographic data as well as economic and medical facts were determined by using questionnaires. In each case a questionnaire was answered by the children or their accompanying persons and a separate one was completed by the respective doctor. RESULTS: The results created a foundation, on the basis of patient volume per day and per daytime. Less than 20% of the children admitted to consult the clinic for their first time. The majority of patients visit them because of a letter of referral. Most of the patients (58%) were younger than 6 years old. Approximately 35% of patients did not come from the city region of Leipzig. CONCLUSION: The investigation evidenced the necessity of a day and night operating institution for children in the region of Leipzig as well as the high specialisation of the outpatient clinic. In need of further investigation is the cooperation between several physicians to find out if this lots of medical examination are necessary or if there took place overlapping.


Assuntos
Hospitais Universitários/estatística & dados numéricos , Hospitais Universitários/normas , Ambulatório Hospitalar/estatística & dados numéricos , Ambulatório Hospitalar/normas , Pediatria/normas , Gestão da Qualidade Total/estatística & dados numéricos , Gestão da Qualidade Total/normas , Adolescente , Plantão Médico/normas , Plantão Médico/estatística & dados numéricos , Criança , Pré-Escolar , Comportamento do Consumidor , Alemanha , Pesquisa sobre Serviços de Saúde , Humanos , Garantia da Qualidade dos Cuidados de Saúde/normas , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/estatística & dados numéricos , Inquéritos e Questionários , Revisão da Utilização de Recursos de Saúde/estatística & dados numéricos
18.
Nucleic Acids Res ; 40(9): 4110-24, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22238380

RESUMO

Human telomerase RNA (hTR) contains several guanine tracts at its 5'-end that can form a G4-quadruplex structure. Previous evidence suggests that a G4-quadruplex within this region disrupts the formation of an important structure within hTR known as the P1 helix, a critical element in defining the template boundary for reverse transcription. RNA associated with AU-rich element (RHAU) is an RNA helicase that has specificity for DNA and RNA G4-quadruplexes. Two recent studies identify a specific interaction between hTR and RHAU. Herein, we confirm this interaction and identify the minimally interacting RNA fragments. We demonstrate the existence of multiple quadruplex structures within the 5' region of hTR and find that these regions parallel the minimal sequences capable of RHAU interaction. We confirm the importance of the RHAU-specific motif in the interaction with hTR and demonstrate that the helicase activity of RHAU is sufficient to unwind the quadruplex and promote an interaction with 25 internal nucleotides to form a stable P1 helix. Furthermore, we have found that a 5'-terminal quadruplex persists following P1 helix formation that retains affinity for RHAU. Finally, we have investigated the functional implications of this interaction and demonstrated a reduction in average telomere length following RHAU knockdown by small interfering RNA (siRNA).


Assuntos
RNA Helicases DEAD-box/metabolismo , Quadruplex G , RNA/química , Telomerase/química , Sítios de Ligação , RNA Helicases DEAD-box/química , RNA Helicases DEAD-box/genética , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Conformação de Ácido Nucleico , RNA/metabolismo , Telomerase/metabolismo , Homeostase do Telômero
19.
Z Gastroenterol ; 52(9): 1066-74, 2014 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-25198086

RESUMO

INTRODUCTION: Capsule endoscopy (CE) is firmly established as a standard procedure in the diagnostic algorithm of mid gastrointestinal (GI) bleeding. Despite its excellent diagnostic yield, missing expertise, reading time and financial expenditure limit an area-wide availability. A multicentric cooperation might compensate these disadvantages. METHODS: The CE device was bought by a centrally located hospital (CH). CE-equipment is transported to the network partner (NP) on request and the procedure performed at the spot. Video reading is exclusively done in the CH. RESULTS: Between January 2002 and July 2013, 1026 CE (548 m, 478f; 64 ±â€Š16, 13 - 93 yrs.) were performed within the network. 744/1026 (73 %) CE were done at 17 NP, 282/1026 (27 %) in the CH. Between 2002 (n = 39) and 2012 (n = 136) the annual number of CE increased threefold. Leading indication for CE was suspected mid GI-bleeding (80 %). Mean latencies between requested date and actual examination were less than 24 h and 2 days between CE performance and report. 95 % of the capital investment in each cooperating hospital could be avoided by sharing one workstation within the network. CONCLUSION: The experience from more than 1000 CE show that long-term multicentric utilization of CE equipment is feasible. Such a network runs at stable procedural quality levels similar to an in-house supply, allows an economic as well as area-wide availability of CE and improves reading expertise by centralized video evaluation.


Assuntos
Endoscopia por Cápsula/estatística & dados numéricos , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/patologia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Setor Privado/estatística & dados numéricos , Programas Médicos Regionais/estatística & dados numéricos , Revisão da Utilização de Recursos de Saúde , Alemanha/epidemiologia , Humanos , Prevalência
20.
bioRxiv ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39211269

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that originate from the incomplete combustion of organic materials. We investigated the clastogenicity and mutagenicity of benzo[ b ]fluoranthene (BbF), one of 16 priority PAHs, in MutaMouse males after a 28-day oral exposure. BbF causes robust dose-dependent increases in micronucleus frequency in peripheral blood, indicative of chromosome damage. Duplex Sequencing (DS), an error-corrected sequencing technology, reveals that BbF induces dose-dependent increases in mutation frequencies in bone marrow (BM) and liver. Mutagenicity is increased in intergenic relative to genic regions, suggesting a role for transcription-coupled repair of BbF-induced DNA damage. At higher doses, the maximum mutagenic response to BbF is higher in liver, which has a lower mitotic index but higher metabolic capacity than BM; however, mutagenic potency is comparable between the two tissues. BbF induces primarily C:G>A:T mutations, followed by C:G>T:A and C:G>G:C, indicating that BbF metabolites mainly target guanines and cytosines. The mutation spectrum of BbF correlates with cancer mutational signatures associated with tobacco exposure, supporting its contribution to the carcinogenicity of combustion-derived PAHs in humans. Overall, BbF's mutagenic effects are similar to benzo[ a ]pyrene, a well-studied mutagenic PAH. Our work showcases the utility of DS for effective mutagenicity assessment of environmental pollutants. Synopsis: We used Duplex Sequencing to study the mutagenicity of benzo[ b ]fluoranthene across the mouse genome. Dose-dependent changes in mutation frequency and spectrum quantify its role in PAH-induced carcinogenicity.

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