RESUMO
Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.
Assuntos
Biomarcadores , Técnicas Biossensoriais , Sulfeto de Hidrogênio , Inflamação , Óxido Nítrico , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Modelos Animais , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Cápsulas/administração & dosagem , Probióticos/metabolismo , Bactérias/metabolismo , Luminescência , Progressão da Doença , Inflamação/diagnóstico , Inflamação/metabolismo , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Sulfeto de Hidrogênio/análise , Sulfeto de Hidrogênio/metabolismo , Tecnologia sem Fio/instrumentação , Administração Oral , Tecnologia de Sensoriamento Remoto/instrumentação , Tecnologia de Sensoriamento Remoto/métodos , Fatores de Tempo , Humanos , Tamanho CorporalRESUMO
OBJECTIVES: The recommended treatment for Eating Disorders (EDs) is multidisciplinary and multimodal. Nonetheless, the complex linkage of the different disciplines involved is not necessarily simple. We analyzed the experience of healthcare professionals faced with psychiatric and psychological symptoms in adolescents with EDs in two "multidisciplinary" inpatient units embedded predominantly in different paradigms - one pediatric and one psychiatric. METHODS: Qualitative analysis of 20 healthcare staff members' interviews from different professional backgrounds working in inpatient units for EDs in Montreal (Canada) and Paris (France). RESULTS: The "Complex patients" theme discusses the need for a global approach to the multiplicity of symptoms presented by these patients. "Management and its limits" describes the daily management of psychiatric symptoms in both units. "Psychiatry and Adolescent medicine: from opposition to collaboration" describes the different levels at which these disciplines work together and how this cooperation may be evolving. CONCLUSIONS: The complex entanglement intrinsic in EDs of the patients' somatic, psychosocial, psychiatric, and adolescent problems requires collaboration between disciplines, but the modalities of this collaboration are multiple and evolve non-linearly in specialized treatment units. A multilevel approach must be offered, with the degree of collaboration (multidisciplinary, interdisciplinary and transdisciplinary) appropriate to the complexity of each adolescent's issues.
Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Psiquiatria , Humanos , Adolescente , Criança , Pacientes Internados , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Unidades Hospitalares , Atitude do Pessoal de SaúdeRESUMO
Materials representing common interstratified clay minerals are shown to be composed of aggregates of fundamental particles. Transmission electron microscopy and x-ray diffraction demonstrate that the x-ray diffraction characteristics of a wide range of interstratification can be modeled experimentally by utilizing materials containing only three types of particles. The data have been incorporated into a new model that regards interstratified clay minerals as populations of fundamental particles whose x-ray diffraction patterns result from interparticle diffraction.
RESUMO
Sockeye salmon Oncorhynchus nerka were used as a model in an artificial fertilization experiment to investigate the relationships between individual adult O. nerka and their offspring. Survival, size and burst swimming ability were assessed in fry of known parentage (adult spawners from the Weaver Creek population, British Columbia, Canada). Maternal identity significantly affected the survival rate of eggs at hatch time, though this effect did not extend to fry life stages. The results were also suggestive of a paternal effect on both egg and fry survival, though this could not be separated from the experimental block design. After 4 months of exogenous feeding, fry mass remained under significant maternal influence, though fork length did not, despite having a high correlation with mass. Burst swimming performance was highly variable among individuals, and was not significantly influenced by maternal identity or individual fry size. Collectively, the findings presented here suggest that maternal, and possibly paternal, effects can be integral components of population dynamics in the early life stages of O. nerka. A good understanding of these factors will be essential for scientists and fisheries managers in developing a more holistic view of population-level spawning success and fry survival.
Assuntos
Tamanho Corporal/fisiologia , Salmão/anatomia & histologia , Salmão/fisiologia , Natação/fisiologia , Animais , Tamanho Corporal/genética , Cruzamento , Feminino , Masculino , Salmão/genética , Análise de SobrevidaRESUMO
In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Endopeptidases/metabolismo , Proteínas de Membrana/metabolismo , Processamento de Proteína Pós-Traducional , Receptores de Superfície Celular , Fatores de Transcrição , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/química , Precursor de Proteína beta-Amiloide/genética , Animais , Ácido Aspártico Endopeptidases , Células Cultivadas , Deleção de Genes , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Presenilina-1 , Presenilina-2 , Estrutura Terciária de Proteína , Receptor Notch1 , TransfecçãoRESUMO
The extent of complex formation between the polyene antibiotic, amphotericin B, and cholesterol or ergosterol was investigated and a method for a quantitative measurement of the complex formation was developed. The effect of experimental conditions on the magnitude of the amphotericin B-sterol interaction and on the selectivity of this interaction showed that there was only a narrow range of solvent composition in which the differential selectivity of amphotericin B towards these two sterols could be observed.
Assuntos
Anfotericina B , Colesterol , Ergosterol , Espectrofotometria Ultravioleta , Análise Espectral/métodosRESUMO
The clearance times of 17 different porphyrin derivatives from SKH:HR-1 mice have been measured using the technique of in vivo fluorescence spectroscopy. This technique monitors the in vivo porphyrin fluorescence observed from the external skin surface. Most hydrophilic porphyrin derivatives show relatively short clearance times, in the order of 2.5-6 h. The dicarboxylic acid porphyrins, proto-, hydroxyethylvinyldeutero- and hematoporphyrin IX have clearance times of 7.8, 12.2 and 14.7 h respectively. The mixture hematoporphyrin derivative has an intermediate clearance time of 12.6 h. N-methylated porphyrins show clearance times in the vicinity of 15-22 h. Monoaspartyl chlorin e6 shows the longest clearance time of all porphyrin derivatives measured (30.3 h).
Assuntos
Porfirinas/farmacocinética , Animais , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Pelados , Estrutura Molecular , Porfirinas/química , Pele/metabolismo , Espectrometria de FluorescênciaRESUMO
The pharmacokinetics of Zn phthalocyanine (ZnPc) encapsulated in dipalmitoyl-phosphatidylcholine (DPPC) liposomes, injected intravenously in Skh:HR-1 nude mice, was monitored by two in vitro techniques and one in vivo technique, all based on fluorescence spectroscopy. The in vitro methods involve either fluorescence measurements on thin tissue sections or on extracts from these tissues. The in vivo method involves the fluorescence measurement at the skin surface. Both in vitro techniques gave similar results which are consistent with previous findings on the pharmacokinetic behavior of ZnPc. The liver and spleen showed rapid ZnPc concentration increases, reaching a maximum level in 30 min. or less post drug administration. Relatively little ZnPc was detected in the skin, fat or muscle, the maximum concentration occurring at 12 h. In vivo fluorescence reached a maximum intensity approx. 6 h post injection at the mid-chest analysis site and at 12 h in the thigh. The in vivo measurements at two different anatomical sites showed pharmacokinetic behavior that reflects an overall integrated fluorescence originating from several tissue sites.
Assuntos
Indóis/farmacocinética , Compostos Organometálicos/farmacocinética , Radiossensibilizantes/farmacocinética , Zinco/farmacocinética , 1,2-Dipalmitoilfosfatidilcolina , Animais , Portadores de Fármacos , Indóis/administração & dosagem , Isoindóis , Lipossomos , Masculino , Camundongos , Camundongos Nus , Compostos Organometálicos/administração & dosagem , Espectrometria de Fluorescência/métodos , Zinco/administração & dosagem , Compostos de ZincoRESUMO
Surface-detected fluorescence spectroscopy can be used to monitor the pharmacokinetics of uptake and clearance of red-absorbing fluorophores such as zinc(II) phthalocyanine (ZnPc) in vivo. When this technique is applied to mice that have been fed on a normal chlorophyll-based diet, and particularly when measurements are performed in the abdominal region, oscillations are sometimes observed superimposed on the pharmacokinetic curve of the ZnPc. An oscillatory signal has also been observed arising from the abdominal region of control mice fed a normal diet but not injected with the ZnPc photosensitizer; this oscillatory component to the signal is reduced when mice are fed a chlorophyll-free diet. The oscillatory signal component has been attributed to fluorescence arising from chlorophyll derivatives (pheophorbide/pheophytin) contained in the rodent food, whose concentration in the measured abdominal region changes substantially with time, presumably due to digestive processes. Thus it is important to be aware of the possibility of such artifactual contributions to in vivo fluorescence pharmacokinetic measurements.
Assuntos
Indóis/farmacocinética , Compostos Organometálicos/farmacocinética , 1,2-Dipalmitoilfosfatidilcolina , Animais , Portadores de Fármacos , Indóis/administração & dosagem , Indóis/análise , Isoindóis , Lipossomos , Camundongos , Camundongos Endogâmicos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/análise , Oscilometria , Espectrometria de Fluorescência/instrumentação , Espectrometria de Fluorescência/métodos , Distribuição Tecidual , Zinco/administração & dosagem , Zinco/análise , Zinco/farmacocinética , Compostos de ZincoRESUMO
Volumetric titration of aqueous solutions of haematoporphyrin IX (HP) yields two inflexion points, whereas four pK values can be obtained via mathematical fitting of the experimental data. Assignment of all pK protonation sites is made. A zwitterion is proposed as the neutral species of HP. Evaluation of the pK values of HP in the presence of sodium dodecyl sulphate (SDS) leads to a drastically altered ionic species distribution. On the basis of the distribution diagrams obtained, a pH-sensitive twofold mechanism is proposed for the selective biodistribution of porphyrin-type photochemotherapeutic agents, one involving tissue distribution and the other involving cell membrane penetration by the neutral zwitterion.
Assuntos
Equilíbrio Ácido-Base , Hematoporfirinas/química , Membrana Celular/metabolismo , Hematoporfirinas/farmacocinética , Concentração de Íons de Hidrogênio , Modelos Químicos , Neoplasias/metabolismo , Dodecilsulfato de Sódio/química , Distribuição TecidualRESUMO
An isolated vertical fracture dislocation of the left tarsal navicular with some comminution was successfully treated with open reduction and internal fixation with a screw. The surgical treatment is described, and early mobilization strongly recommended.
Assuntos
Fraturas Ósseas/cirurgia , Luxações Articulares/cirurgia , Ossos do Tarso/lesões , Adulto , Fixação Interna de Fraturas , Humanos , Masculino , Ossos do Tarso/cirurgiaRESUMO
When leaves of wheat (Triticum aestivum L.) are exposed to a cold hardening temperature, a major accumulation of putrescine (6-9 times) takes place. Spermidine accumulates to a lesser extent and, conversely, spermine decreases slightly. These variations are completely reversible when plants are returned to initial growing conditions. A similar response is obtained with crowns. During cold hardening, arginine decarboxylase activity remains near its initial level while a considerable loss of activity is observed in control plants. Ornithine decarboxylase and diamine oxidase activity levels are not substantially modified by the treatment. Alfalfa (Medicago sativa L.) also accumulates putrescine under low temperature stress, indicating that this phenomenon is not typical of cereals. The physiological significance of this accumulation of putrescine is still unexplained but the results obtained suggest the involvement of polyamines in the biochemical processes of cold hardening.
RESUMO
High (15-25 mM) concentrations of 1,3-diaminopropane, a normally minor derivative of polyamine metabolism, have been observed in vegetative cells of Acanthamoeba castellanii. Trace amounts of a putative polyamine, which chromatographically behaved like norspermidine, were also found. The size of the intracellular pool of 1,3-diaminopropane was inversely related to the ambient osmolality and to the free amino acid levels during osmotic shock experiments. Due to its high concentration in A. castellanii, this diamine may be operative in ionic regulation during environmental stress. 1,3-diaminopropane may substitute for putrescine, a common diamine which was undetectable in A. castellanii.
Assuntos
Amoeba/análise , Diaminas/análise , Concentração Osmolar , Pressão OsmóticaRESUMO
In 72% of 143 patients undergoing a second coronary bypass grafting, mural or occlusive late thrombosis was observed histologically in 69% of 173 resected grafts. Late thrombosis was particularly prevalent in atherosclerotic grafts (80.2% vs. 40.4% in nonatherosclerotic grafts) and was always noted in 16 grafts with aneurysmal dilation. Multivariate analysis of risk factors contributing to late thrombosis indicated that graft atherosclerosis and smoking after graft surgery played important roles. Univariate analysis also showed significantly higher ratios of serum total cholesterol/HDL cholesterol and of serum LDL cholesterol/HDL cholesterol in patients whose grafts were affected by late thrombosis. To prevent late thrombosis of saphenous vein aortocoronary grafts, it appears reasonable that decreasing the ratios of total cholesterol/HDL cholesterol and of LDL cholesterol/HDL cholesterol, refraining from smoking, and controlling other risk factors for atherosclerosis should be advised.
Assuntos
Ponte de Artéria Coronária , Complicações Pós-Operatórias , Veia Safena/transplante , Trombose/etiologia , Arteriosclerose/patologia , Feminino , Oclusão de Enxerto Vascular/cirurgia , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Reoperação , Fatores de Risco , Veia Safena/patologia , Fumar/efeitos adversos , Trombose/sangue , Trombose/patologia , Fatores de TempoRESUMO
The authors describe the presentation, clinical evaluation and treatment of 151 patients (mean age 36.3 years) who presented to an outpatient clinic or the emergency department between Oct. 29, 1984, and Apr. 15, 1985, for a lateral ankle sprain. About 60% of the sprains were considered minor. Although 141 patients underwent simple radiography of the ankle on the first visit, only five fractures were identified. All the fractures were uncomplicated and were treated conservatively. No common criteria could be identified to explain why some patients with sprains of moderate severity were referred to an orthopedist while others were not. Of the 53 patients interviewed, 22 still had some limitation of physical activity 6 weeks after the sprain. The presence of malleolar soft-tissue swelling, pain in the bony structures and inability to bear weight should raise the suspicion of a fracture. If radiography had been limited to patients with these signs, no fracture would have been missed, and radiography would have been avoided in 70 cases.
Assuntos
Traumatismos do Tornozelo , Serviços Médicos de Emergência , Entorses e Distensões/diagnóstico por imagem , Adolescente , Adulto , Idoso , Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/diagnóstico por imagem , Feminino , Fraturas Ósseas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
A new cold-regulated (COR) gene, msa CIC, was isolated by differential screening of a cDNA library from cold-acclimated crowns of alfalfa (Medicago sativa L. cv. Apica). Transcripts of msa CIC were not detectable in unacclimated alfalfa and accumulated to higher levels in cold-acclimated plants of the cold-tolerant cv. Apica than in those of the cold-sensitive cv. CUF-101. The DNA sequence analysis of a full-length cDNA clone revealed that msa CIC encodes for a putative protein (MSACIC) of 166 amino acids with distinct proline-rich and hydrophobic domains. Protein sequence comparisons indicated that MSACIC is similar to a group of bimodular proteins that are developmentally regulated in other plant species.
Assuntos
Adaptação Biológica/genética , Regulação da Expressão Gênica , Genes de Plantas/genética , Medicago sativa/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Temperatura Baixa , DNA Complementar/genética , Medicago sativa/crescimento & desenvolvimento , Dados de Sequência Molecular , Conformação Proteica , RNA Mensageiro/análise , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Treatment of birch (Betula papyrifera Marsh) and alder (Alnus incana (L.) Moench) cell suspension cultures with ABA increased the freezing resistance of the cells. After 7 days of treatment with 10(-5) M ABA, birch cells grown at 23 and 4 degrees C attained an LT(50) of -16.9 and -14.1 degrees C, respectively, whereas control cells had an LT(50) of -9.1 degrees C. In alder cell suspensions, treatment with 10(-5) M ABA at 23 degrees C induced a small increase in freezing resistance from -7.3 to -10.8 degrees C. Exposure to 4 degrees C alone did not induce a significant increase in hardiness in birch cell suspensions. Addition of 10(-5) M ABA to the medium inhibited fresh weight increase over 10 days of 3-g inocula of birch and alder by 70 and 52%, respectively. With the same concentration of ABA in the medium we found different intracellular ABA concentrations in 3- and 6-g inocula. We conclude that the concentration of ABA in the medium does not reflect the intracellular concentration of tissue cultures, and that cultural conditions may influence ABA accumulation by cell cultures.