Nasogastric tube syndrome: A case of vocal cord paralysis due to a nasogastric tube.

Insertion of a nasogastric tube is one of the most common methods of administering nutrition, but can cause vocal cord paralysis.

Oxygenation saturation index in neonatal hypoxemic respiratory failure.

BACKGROUND: This study aimed to assess the validity of the oxygenation saturation index (OSI) and the ratio of oxygen saturation to the fraction of inspired oxygen (FIO2) (S/F ratio) with percutaneous oxygen saturation (OSISpO2 and the Sp/F ratio) and to evaluate the correlation between these values and the oxygen index (OI). It also determined their cut-off values for predicting OI in accordance with neonatal hypoxic respiratory failure severity. METHODS: We reviewed the data of 77 neonates (gestational age 31.7 ± 6.1 weeks; birthweight, 1768 ± 983 g) requiring invasive mechanical ventilation between 2013 and 2020, 1233 arterial blood gas samples in total. We calculated the OI, OSISpO2, OSI with arterial oxygen saturation (SaO2) (OSISaO2), Sp/F ratio, and the ratio of SaO2 to FIO2 (Sa/F ratio). RESULTS: The regression and Bland-Altman analysis showed good agreement between OSISpO2 or the Sp/F ratio and OSISaO2 or the Sa/F ratio. Although a significant positive correlation was found between OSISpO2 and OI, OSISpO2 was overestimated in SpO2 > 98% with a higher slope of the fitted regression line than that below 98% of SpO2. Furthermore, receiver-operating characteristic curve analysis using only SpO2 ≤ 98% samples showed that the optimal cut-off points of OSISpO2 and the Sp/F ratio for predicting OI were: OI 5, 3.0 and 332; OI 10, 5.3 and 231; OI 15, 7.7 and 108; OI 20, 11.0 and 149; and OI 25, 17.1 and 103, respectively. CONCLUSION: The cut-off OSISpO2 and Sp/F ratio values could allow continuous monitoring for oxygenation changes in neonates with the potential for wider clinical applications.

Efficacy and safety of peppermint oil for the treatment in Japanese patients with irritable bowel syndrome: a prospective, open-label, and single-arm study.

BACKGROUND: In Europe, an herbal medicine containing peppermint oil is widely used in patients with irritable bowel syndrome (IBS). In Japan, however, no clinical evidence for peppermint oil in IBS has been established, and it has not been approved as a drug for IBS. Accordingly, we conducted a clinical study to confirm the efficacy and safety of peppermint oil (ZO-Y60) in Japanese patients with IBS. METHODS: The study was a multi-center, open-label, single-arm, phase 3 trial in Japanese outpatients with IBS aged 17-60 years and diagnosed according to the Rome III criteria. The subjects were treated with an oral capsule of ZO-Y60 three times a day before meals, for four weeks. The efficacy of ZO-Y60 was evaluated using the patient's global assessment (PtGA), IBS symptom severity score, stool frequency score, stool form score, and physician's global assessment (PGA). The safety of ZO-Y60 was also assessed. RESULTS: Sixty-nine subjects were treated with ZO-Y60. During the four-week administration of ZO-Y60, the improvement rate of the PtGA was 71.6% (48/67) in week 2 and 85.1% (57/67) in week 4. It was also suggested that ZO-Y60 is effective against any type of IBS (IBS with constipation, IBS with diarrhea, and mixed/unsubtyped IBS). The improvement rate of the PGA was 73.1% (49/67) in week 2 and 85.1% (57/67) in week 4, also confirming the efficacy of ZO-Y60. Adverse events were observed in 14 subjects (20.3%), however, none of these adverse events were categorized as serious. CONCLUSION: The efficacy of treatment was confirmed, subjective symptoms were improved, as was observed in previous clinical studies of ZO-Y60 conducted outside of Japan. All adverse reactions were previously known and were non-serious. These findings suggest that peppermint oil may be effective in the Japanese population and that it has an acceptable safety profile. TRIAL REGISTRATION: JAPIC Clinical Trials Information number: JapicCTI-121727 https://jrct.niph.go.jp/en-latest-detail/jRCT1080221685 . Registration date: 2012-01-10.

Synthesis and Biological Evaluation of a Novel Sugar-Conjugated Platinum(II) Complex Having a Tumor-Targeting Effect.

We designed and synthesized a novel platinum complex conjugated with 2-fluorinated 2-deoxyglucoside, named FGC-Pt, to capitalize on the Warburg effect and metabolic trapping properties of [18F]2-deoxy-2-fluoro-d-glucose ([18F]FDG). Then, we conducted comprehensive in vitro and in vivo studies to evaluate the effects of FGC-Pt. In vitro cytotoxicity assays using HeLa cells revealed that FGC-Pt exhibited concentration-dependent cytotoxicity, even though its cytotoxic effect was less pronounced than that of cisplatin. In the evaluation of in vivo biodistribution in mice, platinum concentration in tumors and major organs (muscle, bone, blood, liver, and kidney) and the ratio of platinum concentration in tumors to major organs following the tail vein injection of FGC-Pt and cisplatin suggest that FGC-Pt is more retained in tumors than in other organs and tends to accumulate in tumors more than cisplatin. Furthermore, an in vivo assessment of the antitumor effect conducted in A549 cell-bearing mice demonstrated that FGC-Pt possesses substantial potential as an antitumor agent. It exhibited a tumor growth-inhibitory effect comparable to that of cisplatin while inducing lower toxicity, as evidenced by lower weight loss after administration. Herein, we successfully produced a novel compound with a tumor-growth-inhibitory effect comparable to that of cisplatin and low toxicity.

Production and synthesis of a novel 191Pt-labeled platinum complex and evaluation of its biodistribution in healthy mice.

We previously reported that our sugar-conjugated platinum complex (cis-dichloro [(2-fluoro-α-d-glucopylanosidyl) propane-1,3-diamine] platinum: FGC-Pt) has low toxicity and tumor growth inhibitory effect comparable to that of cisplatin. We focused on radioactive Pt isotopes in order to analyze the kinetics of FGC-Pt using gamma-ray imaging techniques, assuming that FGC-Pt could be used for chemotherapy in the future. Therefore, in this study, we aimed to develop a non-invasive method to analyze the biodistribution of FGC-Pt using 191Pt-labeled FGC-Pt ([191Pt]FGC-Pt). 191Pt was produced via the (n,2n) reaction induced by accelerator neutrons. [191Pt]FGC-Pt was prepared using two different methods. In the first method, [191Pt]FGC-Pt (method A) was obtained through the accelerator neutron irradiation of FGC-Pt. In the second method, [191Pt]FGC-Pt (method B) was synthesized using [191Pt]K2PtCl4, which was obtained by the accelerator neutron irradiation of K2PtCl4. Highly purified [191Pt]FGC-Pt was obtained using the latter method, which suggests that the synthetic method using a 191Pt-labeled platinum reagent is suitable for the radioactivation of platinum complexes. We also aimed to investigate whether a significant correlation existed between the biodistribution of FGC-Pt and [191Pt]FGC-Pt in healthy mice 24 h after tail vein administration. FGC-Pt and [191Pt]FGC-Pt were similarly distributed in healthy mice, with a higher accumulation in the liver and kidney 24 h post injection. In addition, a significant correlation (p < 0.05, r = 0.92) between the 191Pt radioactivity concentration (%ID/g (gamma counter)) and platinum concentration (%ID/g (ICP-MS)) was observed in 13 organs. These results suggest that 191Pt-labeled compounds, synthesized using radioactive platinum reagents, can be used to confirm the biodistribution of platinum compounds. Our study on the biodistribution of [191Pt]FGC-Pt is expected to contribute to the development of novel platinum-based drugs in the future.

Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.

Currently, gapmer antisense oligonucleotide (ASO) therapeutics are under clinical development for the treatment of various diseases, including previously intractable human disorders; however, they have the potential to induce hepatotoxicity. Although several groups have reported the reduced hepatotoxicity of gapmer ASOs following chemical modifications of sugar residues or internucleotide linkages, only few studies have described nucleobase modifications to reduce hepatotoxicity. In this study, we introduced single or multiple combinations of 17 nucleobase derivatives, including four novel derivatives, into hepatotoxic locked nucleic acid gapmer ASOs and examined their effects on hepatotoxicity. The results demonstrated successful identification of chemical modifications that strongly reduced the hepatotoxicity of gapmer ASOs. This approach expands the ability to design gapmer ASOs with optimal therapeutic profiles.

TogoID: an exploratory ID converter to bridge biological datasets.

MOTIVATION: Understanding life cannot be accomplished without making full use of biological data, which are scattered across databases of diverse categories in life sciences. To connect such data seamlessly, identifier (ID) conversion plays a key role. However, existing ID conversion services have disadvantages, such as covering only a limited range of biological categories of databases, not keeping up with the updates of the original databases and outputs being hard to interpret in the context of biological relations, especially when converting IDs in multiple steps. RESULTS: TogoID is an ID conversion service implementing unique features with an intuitive web interface and an application programming interface (API) for programmatic access. TogoID currently supports 65 datasets covering various biological categories. TogoID users can perform exploratory multistep conversions to find a path among IDs. To guide the interpretation of biological meanings in the conversions, we crafted an ontology that defines the semantics of the dataset relations. AVAILABILITY AND IMPLEMENTATION: The TogoID service is freely available on the TogoID website (https://togoid.dbcls.jp/) and the API is also provided to allow programmatic access. To encourage developers to add new dataset pairs, the system stores the configurations of pairs at the GitHub repository (https://github.com/togoid/togoid-config) and accepts the request of additional pairs. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cardiopulmonary arrest caused by nafamostat mesylate during hemodialysis.

Dialysis-related adverse reactions can be serious and difficult to predict. In our case, nafamostat mesylate (NM) was thought to be the cause of cardiopulmonary arrest (CPA) due to NM-induced anaphylaxis but was not reflected in the allergy tests. Rare but life-threatening drawbacks occur immediately after hemodialysis initiation.

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor.

We have successfully synthesized piperidine and pyrrolidine derivatives by electroreductive cyclization using readily available imine and terminal dihaloalkanes in a flow microreactor. Reduction of the substrate imine on the cathode proceeded efficiently due to the large specific surface area of the microreactor. This method provided target compounds in good yields compared to a conventional batch-type reaction. Furthermore, piperidine and pyrrolidine derivatives could be obtained on preparative scale by continuous electrolysis for approximately 1 hour.

Bayesian optimization with constraint on passed charge for multiparameter screening of electrochemical reductive carboxylation in a flow microreactor.

Multiparameter screening of reductive carboxylation in an electrochemical flow microreactor was performed using a Bayesian optimization (BO) strategy. The developed algorithm features a constraint on passed charge for the electrochemical reaction, which led to suitable conditions being instantaneously found for the desired reaction. Analysis of the BO-suggested conditions underscored the physicochemical validity.

Technical considerations in Hi-C scaffolding and evaluation of chromosome-scale genome assemblies.

The recent development of ecological studies has been fueled by the introduction of massive information based on chromosome-scale genome sequences, even for species for which genetic linkage is not accessible. This was enabled mainly by the application of Hi-C, a method for genome-wide chromosome conformation capture that was originally developed for investigating the long-range interaction of chromatins. Performing genomic scaffolding using Hi-C data is highly resource-demanding and employs elaborate laboratory steps for sample preparation. It starts with building a primary genome sequence assembly as an input, which is followed by computation for genome scaffolding using Hi-C data, requiring careful validation. This article presents technical considerations for obtaining optimal Hi-C scaffolding results and provides a test case of its application to a reptile species, the Madagascar ground gecko (Paroedura picta). Among the metrics that are frequently used for evaluating scaffolding results, we investigate the validity of the completeness assessment of chromosome-scale genome assemblies using single-copy reference orthologues.

Integrated Flow Synthesis of α-Amino Acids by In Situ Generation of Aldimines and Subsequent Electrochemical Carboxylation.

The synthesis of α-amino acids was carried out in a continuous flow system. In this system, aldimines were efficiently generated in situ via the dehydration-condensation of aldehydes with anilines in a desiccant bed column filled with 4 Å molecular sieves desiccant, followed by reaction with CO2 in an electrochemical flow microreactor to afford the α-amino acids in high to moderate yields. The present system can provide α-amino acids without using stoichiometric amounts of metal reagents or highly toxic cyanide reagents.

Reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates with respiratory distress.

Hypercapnia occurs in ventilated infants even if tidal volume (VT) and minute ventilation (VE) are maintained. We hypothesised that increased physiological dead space (Vd,phys) caused decreased minute alveolar ventilation (VA; alveolar ventilation (VA) × respiratory rate) in well-ventilated infants with hypercapnia. We investigated the relationship between dead space and partial pressure of carbon dioxide (PaCO2) and assessed VA. Intubated infants (n = 33; mean birth weight, 2257 ± 641 g; mean gestational age, 35.0 ± 3.3 weeks) were enrolled. We performed volumetric capnography (Vcap), and calculated Vd,phys and VA when arterial blood sampling was necessary. PaCO2 was positively correlated with alveolar dead space (Vd,alv) (r = 0.54, p < 0.001) and Vd,phys (r = 0.48, p < 0.001), but not Fowler dead space (r = 0.14, p = 0.12). Normocapnia (82 measurements; 35 mmHg ≤ PaCO2 < 45 mmHg) and hypercapnia groups (57 measurements; 45 mmHg ≤ PaCO2) were classified. The hypercapnia group had higher Vd,phys (median 0.57 (IQR, 0.44-0.67)) than the normocapnia group (median Vd,phys/VT = 0.46 (IQR, 0.37-0.58)], with no difference in VT. The hypercapnia group had lower VA (123 (IQR, 87-166) ml/kg/min) than the normocapnia group (151 (IQR, 115-180) ml/kg/min), with no difference in VE.Conclusion: Reduction of VA in well-ventilated neonates induces hypercapnia, caused by an increase in Vd,phys. What is Known: • Volumetric capnography based on ventilator graphics and capnograms is a useful tool in determining physiological dead space of ventilated infants and investigating the cause of hypercapnia. What is New: • This study adds evidence that reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates.

Bright and dark sides of exercise effects on biological responses such as energy metabolism and renal function in rats with renal failure and fructose-induced glucose intolerance.

In the present study, we investigated the beneficial and risky effects of exercise intended to prevent or treat lifestyle-related diseases on insulin sensitivity, lactic acid utilization, lipid metabolism, hepatic and renal oxidative stress, hepatic selenoprotein P and renal function in obese and glucose-intolerant rats with renal failure. We fed normal rats a 20% casein diet while the glucose-intolerant, obese rats received a high-fructose diet, and after then rats received single injection of vancomycin at a dose of 400 mg/kg for constructing the duplicative state of renal failure and diabetes mellitus. They were forced to run for 1 h/day, 6 days/week, for 10 weeks. Exercise reduced visceral fat and ameliorated insulin sensitivity in the high-fructose group, improved lactic acid usage efficiency, however, increased hepatic oxidative stress and complicated renal dysfunction in the normal and high-fructose fed groups with renal failure. Additionally, exercise upregulated hepatic selenoprotein P expression and enhanced renal antioxidative system in both groups. It is concluded that strictly controlled exercise conditions must be adapted to patient health states especially in view of kidney protection, and supplemental therapy is also recommended in parallel with exercise, using nutrients and vitamins for kidney protection.

Effects of exercise on biological trace element concentrations and selenoprotein P expression in rats with fructose-induced glucose intolerance.

In the present study, we investigated the effects of exercise intended to prevent or treat lifestyle-related diseases on the glucose tolerance, insulin level, lactic acid utilization, muscle glycogen synthesis, hepatic and renal oxidative stress, hepatic selenoprotein P and biological trace element levels in organs of obese, glucose-intolerant rats. We fed normal, healthy rats a 20% casein diet while the glucose-intolerant, obese rats received a high-fructose diet. They were forced to run for one hour per day, six days per week, for ten weeks. Exercise reduced visceral fat and ameliorated glucose tolerance in the high-fructose group, lowered blood lactic acid levels, improved lactic acid usage efficiency, and increased oxidative stress and hepatic levels of Mn, Fe, Cu, and Zn in the normal and high-fructose groups. Additionally, exercise significantly upregulated hepatic selenoprotein P expression in both groups, however, its effect was remarkable in healthy group. On the other hand, muscle glycogen synthesis was not markedly enhanced in high-fructose-diet rats but in normal-diet rats in response to exercise. It is concluded that exercise conditions rather than exercise load must be customized and optimized for each health and disease states in advance before starting exercise training intended to prevent or treat lifestyle-related diseases.

BioHackathon 2015: Semantics of data for life sciences and reproducible research.

We report on the activities of the 2015 edition of the BioHackathon, an annual event that brings together researchers and developers from around the world to develop tools and technologies that promote the reusability of biological data. We discuss issues surrounding the representation, publication, integration, mining and reuse of biological data and metadata across a wide range of biomedical data types of relevance for the life sciences, including chemistry, genotypes and phenotypes, orthology and phylogeny, proteomics, genomics, glycomics, and metabolomics. We describe our progress to address ongoing challenges to the reusability and reproducibility of research results, and identify outstanding issues that continue to impede the progress of bioinformatics research. We share our perspective on the state of the art, continued challenges, and goals for future research and development for the life sciences Semantic Web.

CRISPR-Cas3 induces broad and unidirectional genome editing in human cells.

Although single-component Class 2 CRISPR systems, such as type II Cas9 or type V Cas12a (Cpf1), are widely used for genome editing in eukaryotic cells, the application of multi-component Class 1 CRISPR has been less developed. Here we demonstrate that type I-E CRISPR mediates distinct DNA cleavage activity in human cells. Notably, Cas3, which possesses helicase and nuclease activity, predominantly triggered several thousand base pair deletions upstream of the 5'-ARG protospacer adjacent motif (PAM), without prominent off-target activity. This Cas3-mediated directional and broad DNA degradation can be used to introduce functional gene knockouts and knock-ins. As an example of potential therapeutic applications, we show Cas3-mediated exon-skipping of the Duchenne muscular dystrophy (DMD) gene in patient-induced pluripotent stem cells (iPSCs). These findings broaden our understanding of the Class 1 CRISPR system, which may serve as a unique genome editing tool in eukaryotic cells distinct from the Class 2 CRISPR system.

Evaluation of off-target effects of gapmer antisense oligonucleotides using human cells.

Antisense oligonucleotide (ASO) has the potential to induce off-target effects due to complementary binding between the ASO and unintended RNA with a sequence similar to the target RNA. Conventional animal studies cannot be used to assess toxicity induced by off-target effects because of differences in the genome sequence between humans and other animals. Consequently, the assessment of off-target effects with in silico analysis using a human RNA database and/or in vitro expression analysis using human cells has been proposed. Our previous study showed that the number of complementary regions of ASOs with mismatches in the human RNA sequences increases dramatically as the number of tolerated mismatches increases. However, to what extent the expression of genes with mismatches is affected by off-target effects at the cellular level is not clear. In this study, we evaluated off-target effects of gapmer ASOs, which cleave the target RNA in an RNase H-dependent manner, by introducing the ASO into human cells and performing microarray analysis. Our data indicate that gapmer ASOs induce off-target effects depending on the degree of complementarity between the ASO and off-target candidate genes. Based on our results, we also propose a scheme for the assessment of off-target effects of gapmer ASOs.

Pituitary apoplexy after cardiac surgery in a 14-year-old girl with Carney complex: a case report.

A 14-year-old girl was referred to our department because of headache and visual impairment following the resection of recurrent cardiac myxoma. Head magnetic resonance imaging (MRI) scan detected an intra- and supra-sellar tumor. Moreover, the patient showed the presence of spotty skin pigmentations on her cheeks and lower lip. Blood examination revealed hypothyrotropinemia, and ultrasonography results revealed multiple thyroid nodules. She was diagnosed with Carney complex (CNC). Her pituitary tumor was suspected as growth hormone (GH)-secreting adenoma, because overgrowth was observed in the patient. However, biochemical examinations, including oral glucose tolerance test, failed to show the characteristic findings of GH-secreting adenoma. In contrast, insulin tolerance test showed GH deficiency. Her visual impairment improved without performing decompression surgery, and the tumor size decreased, as per the MRI findings. Based on clinical course, the patient was diagnosed with pituitary apoplexy in pituitary adenoma, following which she was discharged. At 3 months after discharge, thyrotropin-releasing hormone loading test performed revealed low thyrotropin-stimulating hormone and thyroid hormone levels, and the patient was in a depressed mood. Therefore, l-T4 replacement was initiated, following which her GH secretory capacity gradually improved. Here, we report, to the best of our knowledge, the first case of a patient with pituitary apoplexy in CNC. Such condition must be identified in young patients with recurrent cardiac myxoma, and examinations, such as head MRI, must be performed.

Intentional or unintentional drug poisoning in elderly people: retrospective observational study in a tertiary care hospital in Japan.

AIM: Intentional or unintentional acute drug poisoning occurs even in elderly people, but little is known about the factors influencing the intention to poisoning. A retrospective study was undertaken to describe the characteristics of acute drug poisoning in elderly people according to whether the poisoning was intentional or unintentional and the responsible agents. METHODS: The study was carried out in a single tertiary hospital in Japan. A total of 145 patients aged ≥65 years who were transferred by an ambulance service and were diagnosed with acute drug poisoning were included. Medical records were used to collect information on the intention behind poisoning and the responsible agents. Patients were divided into two groups according to whether they experienced intentional or unintentional poisoning and were further classified according to the responsible agent. Multivariable logistic regression models were used to estimate the association between hospitalization for acute drug poisoning and the use of benzodiazepine receptor agonists (BzRAs). RESULTS: Poisoning was unintentional in 102 (70.3%) patients and intentional in 43 (29.7%) patients. In total, 65 (44.8%) patients required hospitalization. Among patients in the unintentional poisoning group, those using non-BzRAs were more likely to be hospitalized than those using BzRAs (odds ratio, 6.64; 95% confidence interval, 2.56-17.22). The length of hospital stay was significantly longer in the unintentional poisoning group than in the intentional poisoning group (13.9 vs. 6.2 days; P = 0.013). CONCLUSIONS: The proportion of unintentional poisoning in the elderly is high, and particularly with respect to poisoning with non-BzRAs, the hospitalization rates are high.