Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.

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.

The experience of healthcare professionals treating adolescents with eating disorders in psychiatric and pediatric inpatient units for adolescents: A qualitative study.

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.

The 2018 rift eruption and summit collapse of Kilauea Volcano.

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.

Persistent parental effects on the survival and size, but not burst swimming performance of juvenile sockeye salmon Oncorhynchus nerka.

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.

Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations.

The Notch family of proteins consists of transmembrane receptors that play a critical role in the determination of cell fate. Genetic studies in Caenorhabditis elegans suggest that the presenilin proteins, which are associated with familial Alzheimer's disease, regulate Notch signaling. Here we show that proteolytic release of the Notch-1 intracellular domain (NICD), an essential step in the activation of Notch signaling, is markedly reduced in presenilin-1 (PS1)-deficient cells and is restored by PS1 expression. Nuclear translocation of the NICD is also markedly reduced in PS1-deficient cells, resulting in reduced transcriptional activation. Mutations in PS1 that are associated with familial Alzheimer's disease impair the ability of PS1 to induce proteolytic release of the NICD and nuclear translocation of the cleaved protein. These results suggest that PS1 plays a central role in the proteolytic activation of the Notch-1-signaling pathway and that this function is impaired by pathogenic PS1 mutations. Thus, dysregulation of proteolytic function may underlie the mechanism by which presenilin mutations cause Alzheimer's disease.

Differential accumulation of two glycine-rich proteins during cold-acclimation alfalfa.

Two mRNAs, MsaCiA and MsaCiB, encoding for proteins harboring glycine-rich motifs, accumulate in alfalfa during cold acclimation. Fusion polypeptides containing the amino acid sequences deduced from these mRNAs were produced in Escherichia coli and used to raise antibodies. Each antibody cross-reacted specifically with soluble polypeptides, MSACIA-32 and MSACIB, respectively. These polypeptides were detectable only in crowns of cold-acclimated plants, even though MsaCiA mRNA accumulated in both crows and leaves during cold acclimation. The analysis of parietal proteins showed that several MSACIA-related proteins, with a molecular mass of 32, 41 and 68 kDa, did accumulate in leaf cell walls and one of 59 kDa crown cell walls. This diversity is most probably due to a tissue-specific maturation of MSACIA. A discrepancy was found between the time-course of accumulation of MSACIB and the one of the corresponding transcript. These results indicate that timing and localization of MSACIA and MSACIB expression are different, and suggest that this differential expression involves both transcriptional and post-transcriptional events. Comparisons made among six cultivars of contrasting freezing tolerance suggest that low tolerance could be explained by failure to accumulate proteins like MSACIA and MSACIB at a sufficient level.

Changes in ABA and gene expression in cold-acclimated sugar maple.

To determine if cold acclimation of sugar maple (Acer saccharum Marsh.) is associated with specific changes in gene expression under natural hardening conditions, we compared bud and root translatable mRNAs of potted maple seedlings after cold acclimation under natural conditions and following spring dehardening. Cold-hardened roots and buds were sampled in January when tissues reached their maximum hardiness. Freezing tolerance, expressed as the lethal temperature for 50% of the tissues (LT(50)), was estimated at -17 degrees C for roots, and at lower than -36 degrees C for buds. Approximately ten transcripts were specifically synthesized in cold-acclimated buds, or were more abundant in cold-acclimated buds than in unhardened buds. Cold hardening was also associated with changes in translation. At least five translation products were more abundant in cold-acclimated buds and roots compared with unhardened tissues. Abscisic acid (ABA) concentration increased approximately tenfold in the xylem sap following winter acclimation, and the maximum concentration was reached just before maximal acclimation. We discuss the potential involvement of ABA in the observed modification of gene expression during cold hardening.

On the source of the oscillations observed during in vivo zinc phthalocyanine fluorescence pharmacokinetic measurements in mice.

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.

Effects of soil freezing and drought stress on abscisic acid content of sugar maple sap and leaves.

In 1991 and 1992, mature maple trees (Acer saccharum Marsh.) were freeze-stressed or drought-stressed by preventing precipitation (snow or rain) from reaching the forest floor under selected trees. Lack of snow cover caused a decrease in soil temperature to well below 0 degrees C from December to April and a lowering of the soil water content to 10%. The abscisic acid (ABA) concentration in the spring sap of deep-soil frost-stressed trees was significantly higher than in control or drought-stressed trees. The increase in ABA concentration in the xylem sap in the spring of 1991 and 1992 preceded symptoms of canopy decline and a decrease in leaf area that were observed during the summers of 1991 and 1992. These results suggest a role for ABA in root-to-shoot communication in response to environmental stress. The largest differences in ABA concentration induced by the treatments was found in sap collected at the end of sap flow. The increase in ABA concentration in spring sap at the end of the sap flow could be used as an early indicator of stress suffered by trees during the winter. Not only did the increase in ABA concentration occur before any visible symptoms of tree decline appeared, but the trees that showed the most evident decline had the highest ABA concentrations in the spring sap. Leaf ABA concentration was not a good indicator of induced stress.

A cold-induced gene from Medicago sativa encodes a bimodular protein similar to developmentally regulated proteins.

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.

Heat and cold shock protein synthesis in arctic and temperate strains of rhizobia.

We compared heat shock proteins (HSPs) and cold shock proteins (CSPs) produced by different species of Rhizobium having different growth temperature ranges. Several HSPs and CSPs were induced when cells of three arctic (psychrotrophic) and three temperate (mesophilic) strains of rhizobia were shifted from their optimal growth temperatures (arctic, 25 degrees C; temperate, 30 degrees C) to shock temperatures outside their growth temperature ranges. At heat shock temperatures, three major HSPs of high molecular weight (106,900, 83,100, and 59,500) were present in all strains for all shock treatments (29, 32, 36.4, 38.4, 40.7, 41.4, and 46.4 degrees C), with the exception of temperate strains exposed to 46.4 degrees C, in which no protein synthesis was detected. Cell survival of arctic and temperate strains decreased markedly with the increase of shock temperature and was only 1% at 46.4 degrees C. Under cold shock conditions, five proteins (52.0, 38.0, 23.4, 22.7, and 11.1 kDa) were always present for all treatments (-2, -5, and -10 degrees C) in arctic strains. Among temperate strains, five CSPs (56.1, 37.1, 34.4, 17.3, and 11.1 kDa) were present at temperatures down to 0 degrees C. The 34.4- and the 11.1-kDa components were present in all temperate strains at -5 degrees C and in one strain at -10 degrees C. Survival of all strains decreased with cold shock temperatures but was always higher than 50%. These results show that rhizobia can synthesize proteins at temperatures not permissive for growth. In all shock treatments, no correspondence between the number of HSPs or CSPs produced and rhizobial survival was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Clearance times of porphyrin derivatives from mice as measured by in vivo fluorescence spectroscopy.

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).

Effect of ABA on freezing resistance of Betula papyrifera and Alnus incana woody plant cell suspensions.

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.

A comparison of fluorescence methods used in the pharmacokinetic studies of Zn(II)phthalocyanine in mice.

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.

The effect of tissue and cellular pH on the selective biodistribution of porphyrin-type photochemotherapeutic agents: a volumetric titration study.

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.

Value of plasma NH2-terminal fragment of pro-opiomelanocortin in marking human lung cancer in various clinical settings.

Plasma concentration of amino-terminal segment of pro-opiomelanocortin (N-POMC) was measured by radioimmunoassay (RIA) in 144 patients with various forms of lung cancer during pneumonectomy, at different times of the day after being newly diagnosed and serially, throughout their treatment (surgery or chemotherapy) in order to assess its value as a biomarker in this disease. Normal volunteers, coal miners smoking but without known lung diseases, and the patients with diverse pulmonary disorders served as comparison groups. A significant transtumoral gradient of N-POMC was found at surgery in 15 of 57 (26%) patients. Subjects without lung afflictions had significantly lower N-POMC levels than patients with pulmonary diseases (benign or malignant) only when the blood was drawn before breakfast. Furthermore, fasting levels in all subgroups of patients were higher at any time of the day than nonfasting ones. Finally, N-POMC levels did not decrease significantly after successful treatment of lung cancer (by surgery or chemotherapy) but were markedly higher after relapse. These results suggest that N-POMC, despite the fact that it cannot be used to discriminate lung cancer patients from controls, is a biomarker which may predict relapse in patients successfully treated by chemotherapy for their pulmonary neoplasm.

Late thrombosis of saphenous vein coronary bypass grafts related to risk factors.

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.

Effects of Cold Hardening on the Regulation of Polyamine Levels in Wheat (Triticum aestivum L.) and Alfalfa (Medicago sativa L.).

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.

[Evaluation and treatment of lateral ankle sprain in the emergency department: is systematic radiography necessary?]. / Evaluation et traitement de l'entorse externe de la cheville dans un milieu de soins de première ligne: la radiographie systématique est-elle essentielle?

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.