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1.
Chemistry ; : e202402415, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925568

RESUMO

Biradicals are important intermediates in the formation and breaking of a chemical bond. Their use as molecular switches is of particular interest. Much less is known about tetraradicals, which can, for example, consist of two biradical(oid) units. Here we report the synthesis of the first persistent phosphorus-centred tetraradical bound to a transition metal fragment. Starting from a zirconocene complex, rac-(ebthi)ZrCl2 (rac-(ebthi) = 1,2-ethylene-1,10-bis(h5-tetrahydroin-denyl), two cyclo-1,3-diphospha-pentane-1,3-diyls were successfully introduced, which finally led to the isolation of a deep green zircon-cene-bridged bis(biradicaloid) complex (5) that can act as a double molecular switch. Under the influence of light (570 nm), this tetra-radical forms a transannular bond in each of the two five-membered biradical units, leading to the formation of housane 5h. Upon irradiation at 415 nm, the reverse reaction is observed, fully reco-vering tetraradical 5. Through single-crystal-to-single-crystal trans-formation, both stable species of the molecular switch could be structurally characterised using SCXRD. The switching under the influence of light and the activation of molecular hydrogen were analysed in solution using NMR and UV spectroscopy. It was found that the addition of one or two equivalents of molecular hydrogen can be switched on and off by light.

2.
J Can Dent Assoc ; 89: n5, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37562038

RESUMO

The COVID-19 pandemic has resulted in amended regulations and guidelines governing the practice of dentistry and dental hygiene to ensure the protection of both patients and clinicians from transmission of the SARS-CoV-2 virus. These guidelines include changes in personal protective equipment and, under some guidelines, the institution of a fallow period after any aerosol-generating procedure (AGP). This study aimed to investigate the effect of both ventilation and 4-handed dentistry in clinical practice with patients undergoing supportive periodontal therapy (SPT) by air polishing, ultrasonic and hand instrumentation in a closed operatory. We studied 34 patients during SPT using either 2- or 4-handed dentistry in an operatory with either 0 or 20 additional air changes/h (ACH). Under clinical conditions, 20 additional ACH are adequate to eliminate aerosols produced during an SPT and before the cessation of the AGP. The presence of an assistant had no significant effect on the time needed for aerosol particles to return to baseline values following the AGP. This study supports the efficacy of 20 additional ACH during the process of AGP, but does not support the need for an extended fallow period or 4-handed dentistry to provide additional high-volume evacuation throughout the procedure.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Pandemias/prevenção & controle , Aerossóis e Gotículas Respiratórios , Odontologia
3.
Kidney Blood Press Res ; 47(2): 125-134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34781282

RESUMO

INTRODUCTION: In peritoneal dialysis (PD) patients, the peritoneal membrane is affected by glucose-based solutions used as peritoneal dialysate fluids. This exposure leads to changes of the membrane which may eventually culminate in fibrosis and method failure. In vitro or animal studies demonstrated that glucose transporters are upregulated upon exposure to these solutions. Expression studies of glucose transporters in human peritoneum have not been reported yet. METHODS: Expression of SGLT-2, GLUT1, and GLUT3 in human peritoneal biopsies was analyzed by real-time polymerase chain reaction and Western blot analysis. The localization of these glucose transporters in the peritoneum was evaluated by immunohistochemistry using a Histo-Score. RESULTS: Peritoneal biopsies of patients (healthy controls, uremic, PD, and encapsulating peritoneal sclerosis [EPS]) were analyzed. We found evidence of SGLT-2, GLUT1, and GLUT3 expression in the peritoneal membrane. Protein expression of SGLT-2 increases with PD duration and is significantly enhanced in EPS patients. All transporters were predominantly, but not exclusively, located adjacent to the vessel walls of the peritoneal membrane. CONCLUSION: Our study showed that SGLT-2, GLUT1, and GLUT3 were regularly expressed in the human peritoneum. SGLT-2 was particularly upregulated in PD patients with EPS, suggesting that this upregulation may be associated with pathological changes in the peritoneal membrane in this syndrome. Since preclinical studies in mice show that SGLT-2 inhibitors or downregulation of SGLT-2 ameliorated pathological changes in the peritoneum, SGLT-2 inhibitors may be potentially promising agents for therapy in PD patients that could reduce glucose absorption and delay functional deterioration of the peritoneal membrane in the long term.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Animais , Soluções para Diálise , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 3 , Humanos , Camundongos , Peritônio/patologia , Transportador 2 de Glucose-Sódio
4.
Nature ; 538(7626): 495-498, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27680707

RESUMO

Optical spectroscopy of a primordial isotope has traditionally formed the basis for understanding the atomic structure of an element. Such studies have been conducted for most elements and theoretical modelling can be performed to high precision, taking into account relativistic effects that scale approximately as the square of the atomic number. However, for the transfermium elements (those with atomic numbers greater than 100), the atomic structure is experimentally unknown. These radioactive elements are produced in nuclear fusion reactions at rates of only a few atoms per second at most and must be studied immediately following their production, which has so far precluded their optical spectroscopy. Here we report laser resonance ionization spectroscopy of nobelium (No; atomic number 102) in single-atom-at-a-time quantities, in which we identify the ground-state transition 1S01P1. By combining this result with data from an observed Rydberg series, we obtain an upper limit for the ionization potential of nobelium. These accurate results from direct laser excitations of outer-shell electrons cannot be achieved using state-of-the-art relativistic many-body calculations that include quantum electrodynamic effects, owing to large uncertainties in the modelled transition energies of the complex systems under consideration. Our work opens the door to high-precision measurements of various atomic and nuclear properties of elements heavier than nobelium, and motivates future theoretical work.

5.
J Clin Periodontol ; 47(4): 461-469, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31999847

RESUMO

AIMS: Higher intakes of fruits and vegetables, and vitamin C are associated with improved periodontal healing post-scaling and root planing (SRP). This study determined if this association was sustained at 3-4 years post-SRP, and if flavonoid intake is associated with periodontal health. Whether reduced probing depth (PD) is sustained and whether PD is correlated with salivary IL-1ß, IL-6 and CRP at 3-4 years post-SRP were also studied. MATERIALS AND METHODS: Clinical periodontal outcomes, dietary intakes and salivary markers of inflammation were measured in patients (n = 43, 23 females, 37-93 years) who had undergone SRP 3-4 years earlier and had been part of a periodontal maintenance programme. RESULTS: Flavonoid intake was inversely associated with PD (p = .042) and salivary IL-1ß concentration (p = .015) after adjustment for multiple confounders. When changes in PD were considered, the association of flavonoid intake with reduced PD became borderline significant (p = .051) but persisted for IL-1ß (p = .018). PD at 3-4 years and 2-4 months post-SRP was similar. There was a positive correlation between PD and salivary IL-1ß (p = .005) but not with salivary CRP and IL-6. CONCLUSION: Higher flavonoid intake is associated with lower IL-1ß. Also, regular supportive periodontal therapy maintained the improved PD at 3-4 years post-SRP regardless of smoking status.


Assuntos
Flavonoides , Periodontite , Raspagem Dentária , Feminino , Flavonoides/uso terapêutico , Seguimentos , Saúde , Humanos , Manutenção , Periodontite/prevenção & controle , Aplainamento Radicular
6.
J Clin Periodontol ; 45(5): 578-585, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29500837

RESUMO

AIMS: To determine the relationship between anticipated pain and actual pain experienced following soft tissue grafting or implant surgery; to identify the factors that predict actual pain experienced and the use of pain medication following soft tissue grafting or implant surgery. MATERIALS AND METHODS: Prior to dental implant placement (n = 98) or soft tissue grafting (n = 115) and for seven days following the procedure, patients completed a visual analog scale indicating anticipated or experienced pain, respectively. The use of pain medication and alcohol, and smoking were measured. RESULTS: Actual pain experienced on day 1 was lower (p < .01) than anticipated pain and continued to decrease (p ≤ .01) for each of the 7 consecutive days. Anticipated and actual pain were positively correlated. Increasing age (p < .05), having sedation during the surgery (p < .05), and lower use of pain pills (p < .01) predicted lower pain experienced. Actual pain experienced was a predictor of pain pill use (p < .01). Greater nervousness (p < .01) prior to surgery was a predictor of greater anticipated pain. CONCLUSIONS: Patients anticipated more pain than they actually experienced. Sedation, age and number of pain pills used predicted pain experienced. This trial was registered with clinicaltrials.gov as NCT03064178.


Assuntos
Medo , Procedimentos Cirúrgicos Bucais , Medição da Dor , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Doenças Periodontais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Implantes Dentários , Feminino , Gengiva/transplante , Humanos , Masculino , Pessoa de Meia-Idade
7.
Orv Hetil ; 159(45): 1844-1847, 2018 11.
Artigo em Húngaro | MEDLINE | ID: mdl-30415568

RESUMO

Dirofilariasis refers to an infection caused by a specific parasitic roundworm. Dirofilaria repens - transmitted by mosquito bites - accounts for most human cases. The parasite forms a subcutaneous mass called cutaneous dirofilariasis near the original site of intrusion. The incidence of human infections shows an increasing tendency. We report a case of a 35-year-old woman presenting with three-week history of a painful swelling in the temporal region. The initial diagnostic work-up revealed a roundworm embedded in the subcutaneous fat tissue and temporal muscle. Differential diagnosis included erysipelas, herpes zoster, temporal arteritis. The final diagnosis of helminthiasis was established by ultrasound examination. A multidisciplinary consultation including infectious diseases specialist suggested surgical removal of the lesion. The microbiological examination of the specimen confirmed the presence of a female Dirofilaria repens. Orv Hetil. 2018; 159(45): 1844-1847.


Assuntos
Dermatite/patologia , Dirofilariose/patologia , Cabeça/diagnóstico por imagem , Dermatopatias Infecciosas/parasitologia , Adulto , Dermatite/parasitologia , Dirofilariose/parasitologia , Feminino , Humanos , Dermatopatias Infecciosas/patologia
8.
BMC Nephrol ; 18(1): 91, 2017 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-28302075

RESUMO

BACKGROUND: Metallothionein (MTT) is an endogenous antioxidant that can be induced by both zinc (Zn) and ischemia. In kidneys, increased MTT expression exerts a putative protective role in diabetes and hypoxia. Our goal was to further investigate the behavior of MTT under the influence of Zn and hypoxia in vitro and in vivo. METHODS: MTT expression was measured in vitro in cell cultures of proximal tubular cells (LCC-PK1) by immune-histochemistry and real-time PCR after incubation with increasing concentrations of Zn under hypoxic and non-hypoxic conditions. In addition, in vivo studies were carried out in 54 patients to study MTT induction through Zn. This is a sub-study of a prospective, randomized, double-blind trial on prevention of contrast-media-induced nephropathy using Placebo, Zn and N-Acetylcysteine. Blood samples were obtained before and after 2 days p.o. treatment with or without Zn (60 mg). ELISA-based MTT level measurements were done to evaluate the effects of Zn administration. For in vivo analysis, we considered the ratio of MTT to baseline MTT (MTT1/MTT0) and the ratio of eGFR (eGFR1/eGFR0), correspondingly. RESULTS: In vitro quantitative immuno-histochemical analysis (IHC) and real-time PCR showed that at increasing levels of Zn (5, 10, and 15 µg/ml) led to a progressive increase of MTTs: Median (IQR) expression of IHC also increased progressively from 0.10 (0.09-0.12), 0.15 (0.12-0.18), 0.25 (0.25-0.27), 0.59 (0.48-0.70) (p < 0.0001). Median (IQR) expression of PCR: 0.59 (0.51-1.72), 1.62 (1.38-4.70), 3.58 (3.06-10.42) and 10.81 (9.24-31.47) (p < 0.0001). In contrast, hypoxia did not change MTT-levels in vitro (p > 0.05). In vivo no significant differences (p = 0.96) occurred in MTT-levels after 2 days of Zn administration compared with no Zn intake. Nevertheless, there was a significant correlation between MTT (MTT1/MTT0) and eGFR (eGFR1/eGFR0) in case of Zn administration (rho = -0.49; 95%-CI: -0.78 to -0.03; p = 0.04). CONCLUSIONS: We found that Zn did induce MTTs in vitro, whereas hypoxia had no significant impact. In contrast, no significant increase of MTTs was detected after in vivo administration of Zn. However, there was a significant negative correlation between MTT and eGFR in vivo in case of Zn administration, this could indicate a protective role of MTTs in a setting of reduced kidney function, which is possibly influenced by Zn. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00399256 . Retrospectively registered 11/13/2006.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/fisiologia , Rim/efeitos dos fármacos , Rim/metabolismo , Metalotioneína/sangue , Metalotioneína/metabolismo , Zinco/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
9.
Prev Chronic Dis ; 14: E74, 2017 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-28858605

RESUMO

BACKGROUND: Engaging in regular physical activity reduces the likelihood of developing chronic diseases. A community's rates of physical activity are directly connected to its built environment characteristics, which correspondingly affect the chronic disease prevalence of its population. Community planning and design interventions can increase levels of physical activity and reduce chronic disease rates by identifying and removing environmental and policy barriers that may hinder active living. COMMUNITY CONTEXT: Community stakeholder groups of various sizes and in various settings in Indiana are beginning to make changes to their policies, systems, and environments to increase levels of physical activity for residents. METHODS: We conducted day-long active living workshops in cities and towns in Indiana to help organize and support public officials, community-based organizations, and advocates in their efforts to promote policy, system, and environmental (PSE) changes that lead to more active communities. OUTCOME: We found that following a consistent process of holding a community workshop and then conducting ongoing follow-up activities led to PSE changes within 1 year. Communities that hosted active living workshops created identifiable changes by supporting active living goals through policy adoption, the creation of new advisory committees, and new local funding allocations. INTERPRETATION: The collaborative approach in the workshop provides a successful model for communities to build capacity to implement PSE strategies that support active living. This method requires various community stakeholders to work closely together, using a shared approach to make changes that would be difficult to achieve if they were working independently.


Assuntos
Serviços de Saúde Comunitária , Exercício Físico , Política de Saúde , Redes Comunitárias , Planejamento Ambiental , Política Ambiental , Promoção da Saúde , Humanos , Indiana , Avaliação de Programas e Projetos de Saúde
10.
BMC Med Inform Decis Mak ; 17(1): 103, 2017 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-28693559

RESUMO

BACKGROUND: We present a formalized medical knowledge system using a linguistic approach combined with a semantic net. METHOD: Diseases are defined and coded by natural linguistic terms and linked via a complex network of attributes, categories, classes, lists and other semantic conditions. RESULTS: We have isolated more than 4600 disease entities (termed pathosoms using a made-up word) with more than 100.000 attributes sets (termed pathophemes using a made-up word) and a semantic net with more than 140.000 links. All major-medical thesauri like ICD, ICD-O and OPS are included. CONCLUSIONS: Memem7 is a linguistic approach to medical knowledge approach. With the system, we performed a proof of concept and we conclude from our data that our or similar approaches provides reliable and feasible tools for physicians given a formalized history taking is available. Our approach can be considered as both a linguistic game and a third opinion to a set of patient's data.


Assuntos
Bases de Conhecimento , Aplicações da Informática Médica , Terminologia como Assunto , Humanos
11.
Am J Physiol Renal Physiol ; 308(11): F1247-58, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25834072

RESUMO

Peritoneal inflammation and fibrosis are responses to the uremic milieu and exposure to hyperosmolar dialysis fluids in patients on peritoneal dialysis. Cells respond to high osmolarity via the transcription factor nuclear factor of activated T cells (NFAT5). In the present study, the response of human peritoneal fibroblasts to glucose was analyzed in vitro. Expression levels of NFAT5 and chemokine (C-C motif) ligand (CCL2) mRNA were quantified in peritoneal biopsies of five nonuremic control patients, five uremic patients before PD (pPD), and eight patients on PD (oPD) using real-time PCR. Biopsies from 5 control patients, 25 pPD patients, and 25 oPD patients were investigated using immunohistochemistry to detect the expression of NFAT5, CCL2, NF-κB p50, NF-κB p65, and CD68. High glucose concentrations led to an early, dose-dependent induction of NFAT5 mRNA in human peritoneal fibroblasts. CCL2 mRNA expression was upregulated by high concentrations of glucose after 6 h, but, most notably, a concentration-dependent induction of CCL2 was present after 96 h. In human peritoneal biopsies, NFAT5 mRNA levels were increased in uremic patients compared with nonuremic control patients. No significant difference was found between the pPD group and oPD group. CCL2 mRNA expression was higher in the oPD group. Immunohistochemistry analysis was consistent with the results of mRNA analysis. CD68-positive cells were significantly increased in the oPD group. In conclusion, uremia results in NFAT5 induction, which might promote early changes of the peritoneum. Upregulation of NFAT5 in PD patients is associated with NFκB induction, potentially resulting in the recruitment of macrophages.


Assuntos
Quimiocina CCL2/metabolismo , NF-kappa B/metabolismo , Peritônio/metabolismo , Fatores de Transcrição/metabolismo , Uremia/metabolismo , Adulto , Idoso , Células Cultivadas , Quimiocina CCL2/genética , Quimiocinas/metabolismo , Células Epiteliais/metabolismo , Feminino , Glucose/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Ativação Transcricional/fisiologia
12.
J Nutr ; 145(11): 2512-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26423734

RESUMO

BACKGROUND: Periodontitis is a chronic inflammatory disease and a significant risk factor for tooth loss. Although a link between diet and periodontal health exists, the relation between diet and healing after periodontal therapy has yet to be investigated. OBJECTIVE: The objective was to determine whether higher intakes of fruits and vegetables or nutrients with antioxidant or anti-inflammatory activity are associated with greater healing, measured as reduced probing depth (PD), after scaling and root planing (SRP), a cost-effective treatment to manage periodontal disease and prevent tooth loss. METHODS: Patients (63 nonsmokers, 23 smokers) with chronic generalized periodontitis who were undergoing SRP participated. Healing was evaluated based on PD, assessed at baseline and 8-16 wk after SRP. Intakes of fruits, vegetables, ß-carotene, vitamin C, α-tocopherol, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were estimated using the Block 2005 food frequency questionnaire and a supplement questionnaire. Serum 25-hydroxyvitamin D concentrations were also measured. PD (% sites >3 mm) was modeled in multiple linear regression and analysis of covariance by tertile of intake and adjusted for age, sex, body mass index (BMI), baseline PD, examiner, gingival bleeding, and study duration. RESULTS: In nonsmokers, PD was associated with fruit and vegetable, ß-carotene, vitamin C, α-tocopherol, EPA, and DHA intakes (P < 0.05). PD was not significantly associated with ALA intake or serum 25-hydroxyvitamin D concentration. Significant associations that included supplements (ß-carotene, vitamin C, α-tocopherol) were attenuated or lost, depending on the statistical model used. There were no significant associations within the group of smokers. CONCLUSIONS: Dietary intakes of fruits and vegetables, ß-carotene, vitamin C, α-tocopherol, EPA, and DHA are associated with reduced PD after SRP in nonsmokers, but not smokers, with chronic generalized periodontitis. These findings may lead to the development of dietary strategies to optimize healing after periodontal procedures. This trial was registered at clinicaltrials.gov as NCT02291835.


Assuntos
Ácido Ascórbico/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Periodontite/terapia , Fumar/efeitos adversos , alfa-Tocoferol/administração & dosagem , beta Caroteno/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/administração & dosagem , Índice de Massa Corporal , Doença Crônica , Estudos Transversais , Suplementos Nutricionais , Ingestão de Energia , Feminino , Frutas , Humanos , Inflamação/tratamento farmacológico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Fatores de Risco , Inquéritos e Questionários , Verduras , Vitamina D/análogos & derivados , Vitamina D/sangue , Ácido alfa-Linolênico/administração & dosagem
13.
Nephrol Dial Transplant ; 30(2): 245-51, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25313168

RESUMO

BACKGROUND: Puumala virus (PUUV) is the most common species of hantavirus in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute kidney injury (AKI) and thrombocytopenia. The major goals of this study were to provide a clear clinical phenotyping of AKI in patients with NE and to develop an easy prediction rule to identify patients, who are at lower risk to develop severe AKI. METHODS: A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. Data were collected from medical records and prospectively at follow-up visit. Severe AKI was defined by standard criteria according to the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) classification. Fuller statistical models were developed and validated to estimate the probability for severe AKI. RESULTS: During acute NE, 88% of the patients had AKI according to the RILFE criteria during acute NE. A risk index score for severe AKI was derived by using three independent risk factors in patients with normal kidney function at time of diagnosis: thrombocytopenia [two points; odds ratios (OR): 3.77; 95% confidence intervals (CI): 1.82, 8.03], elevated C-reactive protein levels (one point; OR: 3.02; 95% CI: 1.42, 6.58) and proteinuria (one point; OR: 3.92; 95% CI: 1.33, 13.35). On the basis of a point score of one or two, the probability of severe AKI was 0.18 and 0.28 with an area under the curve of 0.71. CONCLUSION: This clinical prediction rule provides a novel and diagnostically accurate strategy for the potential prevention and improved management of kidney complications in patients with NE and, ultimately, for a possible decrease in unnecessary hospitalization in a high number of patients.


Assuntos
Injúria Renal Aguda/virologia , Febre Hemorrágica com Síndrome Renal/virologia , Orthohantavírus/patogenicidade , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/metabolismo , Adulto , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Estudos Transversais , Feminino , Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/metabolismo , Proteinúria/virologia , Fatores de Risco , Índice de Gravidade de Doença , Trombocitopenia/diagnóstico , Trombocitopenia/metabolismo , Trombocitopenia/virologia
14.
Acta Oncol ; 54(9): 1631-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26228661

RESUMO

BACKGROUND: Particle dose distributions are highly sensitive to anatomy changes in the beam path, which may lead to substantial dosimetric deviations. Robust planning and dedicated image guidance together with strategies for online decision making to counteract dosimetric deterioration are thus mandatory. We aimed to develop methods to quantify anatomical discrepancies as depicted by repeated computed tomography (CT) imaging and to test whether they can predict deviations in target coverage. MATERIAL AND METHODS: Dedicated software tools allowed for voxel-based calculations of changes in the water equivalent path length (WEPL) in beam directions. We prepared proton and carbon ion plans with different coplanar beam angle settings on a series of lung cancer patients, for which planning and localization CT scans under high frequency jet ventilation (HFJV) for tumor fixation were performed. We investigated the reproducibility of target coverage between the optimized and recalculated treatment plans. We then studied how different raster scan and planning settings influence the robustness. Finally, we carried out a systematic analysis of the variations in the WEPL along different coplanar beam angles to find beam directions, which could minimize such variations. RESULTS: The Spearman's correlations for the GTV ΔV95 and ΔV98 with the ΔWEPL for the proton plans with a 0° and -45° two-field configuration were 0.701 (p = 0.02) and 0.719 (p = 0.08), respectively. For beam configurations 0° and -90°, or 0° and + 45°, with lower ΔWEPL, the correlations were no significant. The same trends were observed for the carbon ion plans. Increased beam spot overlap reduced dosimetric deterioration in case of large ΔWEPL. CONCLUSION: Software tools for fast online analysis of WEPL changes might help supporting clinical decision making of image guidance. Raster scan and treatment planning settings can help to compensate for anatomical deviations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Carbono/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Radioterapia com Íons Pesados , Ventilação em Jatos de Alta Frequência , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/diagnóstico por imagem , Estadiamento de Neoplasias , Terapia com Prótons , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Software , Tomografia Computadorizada por Raios X
15.
Drug Metab Dispos ; 42(12): 2033-40, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25231932

RESUMO

Targeted chemotherapy for hepatocellular carcinoma (HCC) is impaired by intrinsic and/or acquired drug resistance. Because drugs used in HCC therapy (e.g., anthracyclines or the tyrosine kinase inhibitor sorafenib) are substrates of uptake and/or efflux transporters, variable expression of these transporters at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. In this study, the variability of expression of uptake transporters [organic cation transporter (OCT) 1 and OCT3] and efflux transporters [multidrug resistance 1 (MDR1)/P-glycoprotein, multidrug resistance protein (MRP) 1, MRP2, and breast cancer resistance protein (BCRP)], selected for their implication in transporting drugs used in HCC therapy, was investigated. HCC and corresponding nontumor tissue samples were collected from 24 Japanese patients at the time of surgery. Protein expression was determined by immunohistochemistry. Expression data were correlated with clinicopathological characteristics and patients' outcome (median follow-up, 53 months). Generally, expression was highly variable among individual tumor samples. Yet median expression of OCT1, OCT3, and MDR1 in HCC was significantly lower (1.4-, 2.7-, and 2-fold, respectively) than in nontumor tissue, while expression of MRP2 persisted and BCRP showed a trend of increased levels in HCC. Patients with low BCRP expression had significantly shorter overall and recurrence-free survival times. Results suggest different expression patterns of drug transporters in HCC, which are associated only in part with clinicopathological characteristics. Detailed information on expression of drug transporters in HCC may be promising for individualization and optimization of drug therapy for liver cancer.


Assuntos
Povo Asiático/genética , Transporte Biológico/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana Transportadoras/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas de Neoplasias/genética , Fator 3 de Transcrição de Octâmero/genética , Transportador 1 de Cátions Orgânicos/genética
16.
Nephron Clin Pract ; 128(1-2): 178-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25376624

RESUMO

INTRODUCTION: Simple peritoneal fibrosis and encapsulating peritoneal sclerosis (EPS) are important lesions in the peritoneum of patients on peritoneal dialysis (PD). We have previously described a population of podoplanin-positive myofibroblasts in peritoneal biopsies from patients with EPS. Platelet-derived growth factor receptor-ß (PDGFRß) is a marker of pericytes, and PDGFs might be involved in the fibrotic response of the peritoneum. This study aimed to describe PDGFRß in the human peritoneum. METHODS: In this retrospective analysis, we localized PDGFRß in peritoneal biopsies from patients with EPS (n = 6) and patients on PD without signs of EPS (n = 5), and compared them with normal peritoneum (n = 4) and peritoneum from uremic patients (n = 5). Consecutive sections were stained for smooth-muscle actin (SMA) and podoplanin. Slides were scored semiquantitatively by 2 observers blinded to the diagnosis. RESULTS: PDGFRß was expressed by cells of arterial walls in all biopsies. A prominent population of PDGFRß-positive cells was present in the normal peritoneum, which were SMA negative on consecutive sections. In patients on PD, a high number of PDGFRß were also positive for SMA. In EPS, the majority of podoplanin-positive cells were positive for PDGFRß. In peritoneal biopsies from normal and uremic patients, the expression of SMA was mainly restricted to cells of arterial walls. Podoplanin expression was restricted to lymphatic vessels in normal peritoneum, in uremic patients, and in patients on PD without EPS. CONCLUSIONS: As podoplanin-positive myofibroblasts express PDGFRß, these cells might be related to pericytes (rather than other sources of fibroblasts). PDGFRß might turn out to be a therapeutic target in EPS.


Assuntos
Fibrose Peritoneal/metabolismo , Peritônio/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
J Int Soc Sports Nutr ; 21(1): 2297992, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38151716

RESUMO

BACKGROUND: Sufficient protein intake is essential for adequate physical condition and athletic performance. However, numerous factors can influence the absorption of consumed protein, including timing, type of protein intake, and gut microbiota. In the present study, elite male water polo players consumed a plant-based, vegan protein supplement with (n = 10) or without (n = 10) pre- and probiotics daily during the 31-day study period. METHODS: We determined the anthropometric characteristics and body composition, dietary habits, gut microbiota composition, and blood parameters of the players at the beginning and at the end of the study. Body composition parameters were analyzed using the InBody 970 bioimpedance analyzer. Gut microbiome composition was determined from stool samples by metagenome sequencing. Paired and unpaired t-tests were used to determine differences between body composition and blood parameters within the groups and between the two groups at the two different sampling times. The Wilcoxon test was used to determine the change in bacterial composition during the study. Correlations between changes in body composition, blood parameters, and taxonomic groups were analyzed using a linear correlation calculation. RESULTS: Skeletal muscle mass (p < 0.001), body cell mass (p = 0.002), arm circumference (p = 0.003), and protein mass (p < 0.001) increased, while body fat mass (p = 0.004) decreased significantly in the intervention group which consumed pre- and probiotics in addition to protein supplement. Activated acetate (reductive TCA cycle I) and propionate (pyruvate fermentation to propanoate I) pathways correlated positively with increased skeletal muscle mass (p < 0.01 and p < 0.05), and the relative abundance of butyrate-producing species showed a significant positive correlation with changes in body fat mass in the intervention group (p < 0.05). These correlations were not observed in the control group without the intake of pre- and probiotics. CONCLUSIONS: The composition of the gut microbiota may influence protein absorption and therefore body composition and consequently physical condition and sports performance.


Assuntos
Desempenho Atlético , Microbioma Gastrointestinal , Probióticos , Humanos , Suplementos Nutricionais , Antropometria , Composição Corporal
18.
Nephrol Dial Transplant ; 28(4): 1021-30, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22734107

RESUMO

BACKGROUND: Chronic peritoneal dialysis (PD) can be complicated by encapsulating peritoneal sclerosis (EPS), the most severe complication associated with long-term PD. METHODS: In this study, we retrospectively analysed 49 EPS patients regarding clinical presentation, histopathological findings, treatment and long-term clinical outcome at our referral centre. Patients were divided into two clinical categories: severe and mild/moderate. RESULTS: All patients in the severe group and most patients in the mild/moderate group had symptoms consistent with EPS. The most common computed tomographic findings were peritoneal thickening in both groups. Small bowel dilatation was frequently present in the severe group. The time of onset of symptoms consistent with EPS to the surgical procedure was median 5 months with an inter-quartile range of 2-12 months in the severe group. To date, 25 of 31 patients in the severe group (follow-up 45.6 ± 39.0 months after surgery) are alive. In the mild/moderate group, 8 of 11 patients are alive (follow-up 41.6 ± 21.6 months). The histological features were consistent with EPS in all biopsies. CONCLUSIONS: The outcome of patients even with severe EPS is not worse. It is a precondition that these patients are treated in specialized referral centres. The time of first clinical symptoms consistent with EPS to requirement of surgery is very short. Earlier diagnosis of the disease is mandatory, even in asymptomatic patients.


Assuntos
Falência Renal Crônica/complicações , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/etiologia , Feminino , Seguimentos , Alemanha , Humanos , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Fibrose Peritoneal/mortalidade , Fibrose Peritoneal/prevenção & controle , Prognóstico , Encaminhamento e Consulta , Estudos Retrospectivos , Taxa de Sobrevida
19.
Kidney Blood Press Res ; 37(1): 84-94, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23552627

RESUMO

BACKGROUND/AIMS: Secondary hyperparathyroidism (sHPT) is known as a very common complication in patients with chronic kidney disease, and G-protein-coupled calcium-sensing receptor (CaSR), Vitamin D receptor (VDR) and Fibroblast growth factor receptor (FGFR)/Klotho complexes seem to be involved in its development. METHODS: Hyperplastic parathyroid glands from 70 sHPT patients and normal parathyroid tissue from 7 patients were obtained during parathyroidectomy. Conventional morphological and immunohistochemical analysis of parathyroid glands was performed after dividing each slide in a 3x3 array. RESULTS: The presence of lipocytes in the normal parathyroid gland and tissue architecture (nodal in patients with sHPT) allows for discrimination between normal parathyroid glands and parathyroid glands of patients with sHPT. Protein expression of Klotho, FGFR, CaSR and VDR was higher in the normal parathyroid glands compared to the sHPT group (p<0.001, p=0.07, p =0.01 and p=0.001). The variability of each protein expression within each tissue slide was high. Therefore correlations between the different immunohistochemical variables were analyzed for each of the nine fields and than analyzed for all patients. Using this analysis, a highly significant positive correlation could be found between the expression of FGFR and VDR (p=0.0004). Interestingly, in terms of VDR we found a shift to a more mixed nuclear/cytoplasmic staining in the HPT group compared to normal parathyroid gland cells, which showed solitary nuclear staining for VDR (p>0.05). CONCLUSIONS: CaSR, VDR and an impaired Klotho-FGFR-axis seem to be the major players in the development of sHPT. Whether the detected correlation between FGFR and VDR and the shift to a more mixed nuclear/cytoplasmic staining of VDR will yield new insights into the pathogenesis of the disease has to be evaluated in further studies.


Assuntos
Glucuronidase/biossíntese , Hiperparatireoidismo Secundário/metabolismo , Glândulas Paratireoides/metabolismo , Receptores de Calcitriol/biossíntese , Receptores de Detecção de Cálcio/biossíntese , Receptores de Fatores de Crescimento de Fibroblastos/biossíntese , Adulto , Idoso , Biomarcadores/metabolismo , Feminino , Humanos , Hiperparatireoidismo Secundário/patologia , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia
20.
J Oral Maxillofac Surg ; 71(1): e15-23, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23099224

RESUMO

PURPOSE: This report describes a fully digital workflow for computer-assisted esthetic facial surgery planning and guidance. MATERIAL AND METHODS: Using optical scans, virtual surgery is performed according to the 3-dimensional cephalometric results. Next, surgical templates are generated using rapid prototyping. These templates act as a guide during surgery. RESULTS: The workflow has been tested successfully in 4 esthetic facial surgical procedures (rhinoplasty and genioplasty). In addition to surgical assistance, the advantages of the workflow include the possibility of discussing the treatment plan interactively with the patient and comparing and measuring simulation surgery with the actual outcome. As an additional benefit, the appropriate size of the alloplastic implants can be determined preoperatively. CONCLUSIONS: Templates could improve special procedures in esthetic facial surgery.


Assuntos
Mentoplastia/métodos , Processamento de Imagem Assistida por Computador , Rinoplastia/métodos , Cirurgia Assistida por Computador , Adulto , Cefalometria , Fissura Palatina/cirurgia , Feminino , Humanos , Imageamento Tridimensional/métodos , Osteotomia de Le Fort , Procedimentos de Cirurgia Plástica , Cirurgia Assistida por Computador/métodos
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