Pregnancy and breastfeeding pose a unique challenge to drug development and clinical application. In addition to drug toxicity to the fetus in utero and infants through breastfeeding, alterations of ...pharmacokinetics in those women also need careful attention. How do we turn around the overall lack of drug efficacy and toxicity information for pregnant and breastfeeding women?
Drugs for Children Ito, S
Clinical pharmacology and therapeutics,
June 2017, Letnik:
101, Številka:
6
Journal Article
Recenzirano
The “Therapeutic Orphan” status of children is gradually improving, but our efforts to eliminate off‐label/off‐evidence use must be sustained for safer and more effective pediatric drug therapy. This ...is even more important in resource‐scarce settings, because of the increasing child population in those regions. The juncture of pediatric pharmacology and global child health represents an emerging field of clinical pharmacology illuminating a crucial societal need on a global scale.
Children: Are We Doing Enough? Ito, S
Clinical pharmacology and therapeutics,
09/2015, Letnik:
98, Številka:
3
Journal Article
Recenzirano
Use of medicines in children is often off‐label or off‐evidence because essential information is lacking. Over the last two decades, consistent efforts have been made to render the regulatory ...framework more amenable to the needs of the pediatric population. Methodological progress is also evident. However, the consistent effort must be sustained.
Bacterial wilt is a serious problem affecting many important food crops. Recent studies have indicated that treatment with biotic or abiotic stress factors may increase the resistance of plants to ...bacterial infection. This study investigated the effects of magnesium oxide nanoparticles (MgO NP) on disease resistance in tomato plants against Ralstonia solanacearum, as well as its antibacterial activity. The roots of tomato seedlings were inoculated with R. solanacearum and then immediately treated with MgO NP; the treated plants showed very little inhibition of bacterial wilt. In contrast, when roots were drenched with a MgO NP suspension prior to inoculation with the pathogen, the incidence of disease was significantly reduced. Rapid generation of reactive oxygen species such as O₂ ⁻˙ radicals was observed in tomato roots treated with MgO NP. Further O₂ ⁻˙ was rapidly generated when tomato plant extracts or polyphenols were added to the MgO NP suspension, suggesting that the generation of O₂ ⁻˙ in tomato roots might be due to a reaction between MgO NP and polyphenols present in the roots. Salicylic acid‐inducible PR1, jasmonic acid‐inducible LoxA, ethylene‐inducible Osm, and systemic resistance‐related GluA were up‐regulated in both the roots and hypocotyls of tomato plants after treatment of the plant roots with MgO NP. Histochemical analyses showed that β‐1,3‐glucanase and tyloses accumulated in the xylem and apoplast of pith tissues of the hypocotyls after MgO NP treatment. These results indicate that MgO NP induces systemic resistance in tomato plants against R. solanacearum.
Abstract
We report the systematic analysis of knots, hotspots, and lobes in 57 active galactic nuclei (AGNs) to investigate the variation of the magnetic field along the jet from the sub-parsec base ...to the terminus on kiloparsec-to-megaparsec scales. Expanding the number of radio/X-ray samples in the work of Kataoka & Stawarz, we analyzed the data in 12 FR
i
and 30 FR
ii
radio galaxies, 12 quasars, and three BL Lac objects, which contained 76 knots, 42 hotspots, and 29 radio lobes. We first derived the equipartition magnetic fields in the cores and then estimated those in various jet components by assuming
B
est
∝
d
−1
, where
d
is the distance from the jet base. On the other hand, the magnetic field in large-scale jets (knots, hotspots, and lobes),
B
eq
, can be estimated from the observed flux and spatial extent under the equipartition hypothesis. We show that the magnetic field decreases as the distance along the jet increases, but generally in a more gentle way than ∝
d
−1
. The increase in
B
eq
/
B
est
at large
d
may suggest the deceleration of the jet downstream, but there is no difference between FR
i
and FR
ii
jets. Moreover, the magnetic fields in the hotspots are systematically larger than those in knots and lobes. Finally, we applied the same analysis to knots and lobes in Centaurus A to check whether the above discussion will hold even in a
single
jet source.
Hair colour is one of the most conspicuous phenotypes in humans, ranging from black, brown, blond to red. This diversity arises mostly from the quantity and ratio of the black‐dark brown eumelanin ...and the reddish‐brown pheomelanin. To study the chemical basis underlying the diversity of hair colour, we have developed several chemical methods to quantify those two pigments. Alkaline H2O2 oxidation affords pyrrole‐2,3,5‐tricarboxylic acid (PTCA) as a eumelanin marker and thiazole‐2,4,5‐tricarboxylic acid (TTCA) as a pheomelanin marker. Pheomelanin can also be analysed as 4‐amino‐3‐hydroxyphenylalanine (4‐AHP) after hydroiodic acid hydrolysis. Using those methods, we evaluated the contents of eumelanin and pheomelanin (the ‘chemical’ phenotype) in human hairs of black, dark brown, brown, light brown, blond and red colour (the ‘visual’ phenotype). Eumelanin contents decrease in that order, with a trace but constant level of pheomelanin, except for red hair which contains about equal levels of pheomelanin and eumelanin. Thus, the chemical phenotype correlates well with the visual phenotype. The genotype of melanocortin‐1 receptor (MC1R), a gene regulating the red hair phenotype, is predictive of hair melanin expressed as the log value of eumelanin to pheomelanin ratio, with a dosage effect evident. Hair melanin contents were also analysed in patients with various hypopigmentary disorders including Hermansky–Pudlak syndrome, Menkes disease, proopiomelanocortin deficiency, cystinosis, malnutrition and trace metal deficiency. The chemical phenotype helped evaluate the precise effects of each disease on pigmentation. In studies of human hair, the chemical phenotype will find more and more application as an objective measure of pigmentation.
Biotransformation Ito, S
Clinical pharmacology and therapeutics,
September 2014, Letnik:
96, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Because the threat of infectious diseases can cause widespread fear in a community, these diseases receive much public attention. Collaborations that bring together industry, academia, regulators, ...and the public can lead to improved and accelerated drug development. The collaborations must be grounded in strong science and expertise in clinical trials. Development of drugs to treat infections caused by resistant bacteria, drugs to treat hepatitis C virus (HCV), and drugs to prevent HIV is taking advantage of these collaborations.
Clinical Pharmacology & Therapeutics (2014); 96 3, 281–283. doi:10.1038/clpt.2014.133
SUMMARY
Reconstruction of the distribution of ground motion due to an earthquake is one of the key technologies for the prediction of seismic damage to infrastructure. Particularly, the immediate ...reconstruction of the spatially continuous wavefield is valuable for decision-making of disaster response decisions in the initial phase. For a fast and accurate reconstruction, utilization of prior information is essential. In fluid mechanics, full-state recovery, which recovers the full state from sparse observation using a data-driven model reduced-order model, is actively used. In this study, the framework developed in the field of fluid mechanics is applied to seismic wavefield reconstruction. A seismic wavefield reconstruction framework based on compressed sensing using the data-driven reduced-order model (ROM) is proposed and its characteristics are investigated through numerical experiments. The data-driven ROM is generated from the data set of the wavefield using the singular value decomposition. The spatially continuous seismic wavefield is reconstructed from the sparse and discrete observation and the data-driven ROM. The observation sites used for reconstruction are effectively selected by the sensor optimization method for linear inverse problems based on a greedy algorithm. The proposed framework was applied to simulation data of theoretical waveform with the subsurface structure of the horizontally stratified three layers. The validity of the proposed method was confirmed by the reconstruction based on the noise-free observation. Since the ROM of the wavefield is used as prior information, the reconstruction error is reduced to an approximately lower error bound of the present framework, even though the number of sensors used for reconstruction is limited and randomly selected. In addition, the reconstruction error obtained by the proposed framework is much smaller than that obtained by the Gaussian process regression. For the numerical experiment with noise-contaminated observation, the reconstructed wavefield is degraded due to the observation noise, but the reconstruction error obtained by the present framework with all available observation sites is close to a lower error bound, even though the reconstructed wavefield using the Gaussian process regression is fully collapsed. Although the reconstruction error is larger than that obtained using all observation sites, the number of observation sites used for reconstruction can be reduced while minimizing the deterioration and scatter of the reconstructed data by combining it with the sensor optimization method. Hence, a better and more stable reconstruction of the wavefield than randomly selected observation sites can be realized, even if the reconstruction is carried out with a smaller number of observations with observation noise, by combining it with the sensor optimization method.
Background
Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the ...presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS.
Methods
This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS.
Results
We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti‐inflammatory drugs intolerance were associated significantly with recurrence.
Conclusion
We subdivided CRSwNP in non‐ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.
Background
The optimal surgical approach for treatment of oesophagogastric junction (OGJ) cancer is controversial. A randomized clinical trial (JCOG9502) comparing transhiatal (TH) and left ...thoracoabdominal (LTA) approaches was stopped after the first interim analysis owing to limited efficacy for LTA resections. Complete 10‐year follow‐up data are now available.
Methods
Patients with histologically proven adenocarcinoma of the OGJ or gastric cardia with oesophageal invasion of 3 cm or less were randomized to a TH or LTA approach. Both groups underwent total gastrectomy and splenectomy with D2 nodal dissection plus para‐aortic lymphadenectomy above the left renal vein. For LTA, a thorough mediastinal lymphadenectomy below the left inferior pulmonary vein was also mandatory. The primary endpoint was overall survival.
Results
A total of 167 patients (82 TH, 85 LTA) were enrolled. The 10‐year overall survival rate was 37 (95 per cent c.i. 26 to 47) per cent for the TH approach and 24 (15 to 34) per cent for the LTA technique (P = 0·060). The hazard ratio for death was 1·42 (0·98 to 2·05) for the LTA technique. Subgroup analysis based on the Siewert classification indicated non‐significant survival advantages in favour of the TH approach.
Conclusion
LTA resections should be avoided in the treatment of adenocarcinoma of the OGJ or gastric cardia. Registration number: NCT00149266 (https://www.clinicaltrials.gov).
No survival benefit from a more extensive operation
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