Shortened lifespan induced by a high-glucose diet is associated with intestinal immune dysfunction in Drosophila sechellia.

Organisms can generally be divided into two nutritional groups: generalists that consume various types of food and specialists that consume specific types of food. However, it remains unclear how specialists adapt to only limited nutritional conditions in nature. In this study, we addressed this question by focusing on Drosophila fruit flies. The generalist Drosophila melanogaster can consume a wide variety of foods that contain high glucose levels. In contrast, the specialist Drosophila sechellia consumes only the Indian mulberry, known as noni (Morinda citrifolia), which contains relatively little glucose. We showed that the lifespan of D. sechellia was significantly shortened under a high-glucose diet, but this effect was not observed for D. melanogaster. In D. sechellia, a high-glucose diet induced disorganization of the gut epithelia and visceral muscles, which was associated with abnormal digestion and constipation. RNA-sequencing analysis revealed that many immune-responsive genes were suppressed in the gut of D. sechellia fed a high-glucose diet compared with those fed a control diet. Consistent with this difference in the expression of immune-responsive genes, high glucose-induced phenotypes were restored by the addition of tetracycline or scopoletin, a major nutritional component of noni, each of which suppresses gut bacterial growth. We propose that, in D. sechellia, a high-glucose diet impairs gut immune function, which leads to a change in gut microbiota, disorganization of the gut epithelial structure and a shortened lifespan.

Radial peripapillary capillary density in superior segmental optic hypoplasia measured with OCT angiography.

BACKGROUND: To investigate the diagnostic power of radial peripapillary capillary (RPC) density, measured with optical coherence tomography angiography (OCT-A), in patients with superior segmental optic hypoplasia (SSOH). METHODS: Forty subjects with SSOH and 40 age- and axial length-matched control subjects were retrospectively registered for this study. SSOH was defined as intraocular pressure less than 21 mmHg with the presence of two of the following: superior rim thinning, superior entrance of the central retinal artery, scleral halo, and pale optic disc; as well as non-progressive visual field loss. RPC density was measured with swept-source OCT-A (Triton, Topcon) overall, in the quadrants, and in the 12 clock-wise sectors. Changes in RPC density were also compared in SSOH patients and age-matched patients with mild- or moderate-stage of glaucoma. RPC density was compared in pairs of groups with Welch's t-test. Diagnostic power was assessed with the area under the receiver operating characteristics curve (AUC). RESULTS: Overall cpRNFLT was significantly different in the normal (106.7 ± 9.5 µm) and SSOH (77.2 ± 13.7 µm, p <  0.001) subjects. RPC density overall and in the superior, nasal, and inferior quadrants was significantly lower in the SSOH group (all, p <  0.001), but not in the temporal (p = 0.756) quadrant. The diagnostic power of RPC density was highest in the superior quadrant (AUC = 0.928) and the 1 o'clock sector (0.896). Comparing the SSOH and glaucoma patients showed that there were no significant differences in RPC density either overall (p = 0.391) or in the superior quadrant (p = 0.268), while RPC density was significantly higher in the inferior (p = 0.005) and temporal quadrants (p <  0.001) and lower in the nasal quadrant (p = 0.029). CONCLUSIONS: Low RPC density was found in the three non-temporal quadrants of the optic nerve head in SSOH patients, in comparison to normal subjects. Regionally, RPC density in SSOH was lower in the nasal quadrant and higher in the inferior and temporal quadrants in comparison to glaucoma patients. Measuring RPC density with OCT-A may help the diagnosis of SSOH and may improve the management of glaucoma.

A quality management system aiming to ensure regulatory-grade data quality in a glaucoma registry.

BACKGROUND: Disease/patient registries are underutilized despite their multiple advantages over clinical trials in the clinical evaluation of drugs, such as the capacity for long-term curation, provision of patient outcome data in routine clinical practice, and provision of benchmark data for comparison. Ensuring the fit-for-purpose quality of data generated from such registries is important to informing regulatory decision making. Here, we report the construction of a quality management system aiming to ensure regulatory-grade data quality for a registry of Japanese patients with glaucoma to evaluate long-term patient outcomes. METHODS: The quality management system was established by reference to the risk-based approach in the ICH-E6 (R2) recommendations. The following three-component approach was taken: establishment of governance, computerized system validation (CSV), and implementation of risk assessment and control. Compliance of the system with the recommendations of regulatory guidelines relevant to use of the registry was assessed. RESULTS: Governance by academic collaboration was established. This was followed by the development of a total of 15 standard operating procedures, including CSV, data management, monitoring, audit, and management of imaging data. The data management system was constructed based on a data management plan, which specified data/paper flow and data management procedures. The electronic data capture (EDC) system was audited by an external vendor, and configured and validated using the V-model framework as recommended in the GAMP5 guideline. Informed consent, eligibility assessment and major ophthalmology measurements were determined as Critical to Quality (CTQ) factors. A total of 22 risk items were identified and classified into three categories, and operationalized in the form of a risk control plan, which included training sessions and risk-based monitoring. The glaucoma registry addressed most quality recommendations in official guidelines issued by multiple health authorities, although two recommendations were not met. CONCLUSIONS: We established and configured a quality management system for a glaucoma registry to ensure fit-for-purpose data quality for regulatory use, and to curate long-term follow-up data of glaucoma patients in a prospective manner.

[The obstruction of a port catheter during the induction of anesthesia].

A 44-year-old woman receiving home hyperalimetation with an implanted port catheter, was scheduled to undergo resection of ovarian cyst and adhesiotomy. For the induction of anesthesia, fentanyl 0.05 mg, thiopental sodium 200 mg, saline 5 ml and vecuronium 10 mg were given through the port catheter. Although she fell asleep, she kept breathing spontaneouly. It was not possible to give any further drugs through this port catheter, suggesting obstruction of the catheter. The endotracheal intubation was assisted with sevoflurane 5% and suxamethonium 80 mg chloride given through the peripheral vein. Five ml of saline used to flash out thiopental sodium before the administration of vecuronium blomide was not considered to be adequate. An experiment was conducted to investigate how much saline is necessary to wash out completely the drug given previously. The results suggest that more than 10 ml of saline should be given through the port catheter. Various types of central venous catheters are being used. Precise knowledge of each catheter is necessary to use this indispensable central vein route, especially at the crucial timing, such as the induction of anesthesia.

Prevalence of Arcobacter species in retail meats and antimicrobial susceptibility of the isolates in Japan.

A survey was conducted to examine the prevalence of Arcobacter species among meat samples and to investigate the antimicrobial susceptibility of the isolates in Japan. In 1998 and 1999, samples of beef (n=90), pork (n=100) and chicken meat (n=100) were purchased from seven retail shops. Arcobacter species were isolated from 2.2%, 7.0% and 23.0% of beef, pork and chicken meat samples, respectively. The rate of isolations in chicken meats was shown to be significantly higher than those of beef and pork. Species-specific polymerase chain reaction (PCR) demonstrated that the most dominant Arcobacter species was Arcobacter butzleri among the isolates examined. Multiple contaminations with different Arcobacter species were observed in 5% of the chicken samples. Almost all the strains tested showed resistance to vancomycin (100%) and methicillin (97.5%). Strains resistant to cephalothin, sulfamethoxazole-trimethoprim, nalidixic acid and chloramphenicol were detected at the rate of 81.1%, 67.2%, 53.5% and 24.6%, respectively. All Arcobacter strains examined were susceptible to ampicillin, tetracycline, streptomycin and kanamycin.

[Application of bispectral index (BIS) monitoring to anesthetic management of posterior spinal fusion in a patient with Duchenne muscular dystrophy].

A 12-year-old boy with Duchenne muscular dystrophy underwent posterior spinal fusion for progressive scoliosis. Preoperative evaluation was focused on respiratory function as well as cardiac function, which revealed markedly reduced respiratory reserve (FVC 0.77 l, %FVC 25.9%, FEV1.0 0.48 l, %FEV1.0 62%) and well-preserved biventricular function. A possible association between malignant hyperthermia and Duchenne muscular dystrophy has been documented. Thus anesthesia was administered without triggering agents. Propofol and fentanyl were used for induction and maintenance of anesthesia, and the patient was ventilated with O2-nitrous oxide mixture. The anesthesia machine, prepared by using a disposable circuit and fresh CO2-absorbent and disconnecting the vaporizers, was flushed with O2 at a rate of 10 l.min-1 for 20 minutes before use. A small dose of vecuronium was administered while monitoring the train-of-four ratio. The bispectral index (BIS) was utilized to optimize the depth of anesthesia so that the wake-up test could be performed promptly on surgeon's request while avoiding the intraoperative awareness. The BIS was helpful in continuously assessing the wakening process. BIS increased from 40's to 80's in 15 minutes after discontinuation of propofol and nitrous oxide during the test. The patient was kept under close observation postoperatively without any sign of malignant hyperthermia.

Ca(2+) homeostasis, Ca(2+) signalling and somatodendritic vasopressin release in adult rat supraoptic nucleus neurones.

Multiple mechanisms that maintain Ca(2+) homeostasis and provide for Ca(2+) signalling operate in the somatas and neurohypophysial nerve terminals of supraoptic nucleus (SON) neurones. Here, we examined the Ca(2+) clearance mechanisms of SON neurones from adult rats by monitoring the effects of the selective inhibition of different Ca(2+) homeostatic molecules on cytosolic Ca(2+) ([Ca(2+)](i)) transients in isolated SON neurones. In addition, we measured somatodendritic vasopressin (AVP) release from intact SON tissue in an attempt to correlate it with [Ca(2+)](i) dynamics. When bathing the cells in a Na(+)-free extracellular solution, thapsigargin, cyclopiazonic acid (CPA), carbonyl cyanide 3-chlorophenylhydrazone (CCCP), and the inhibitor of plasma membrane Ca(2+)-ATPase (PMCA), La(3+), all significantly slowed down the recovery of depolarisation (50 mM KCl)-induced [Ca(2+)](i) transients. The release of AVP was stimulated by 50 mM KCl, and the decline in the peptide release was slowed by Ca(2+) transport inhibitors. In contrast to previous reports, our results show that in the fully mature adult rats: (i) all four Ca(2+) homeostatic pathways, the Na(+)/Ca(2+) exchanger, the endoplasmic reticulum Ca(2+) pump, the plasmalemmal Ca(2+) pump and mitochondria, are complementary in actively clearing Ca(2+) from SON neurones; (ii) somatodendritic AVP release closely correlates with intracellular [Ca(2+)](i) dynamics; (iii) there is (are) Ca(2+) clearance mechanism(s) distinct from the four outlined above; and (iv) Ca(2+) homeostatic systems in the somatas of SON neurones differ from those expressed in their terminals.