Bioavailability of black tea theaflavins: absorption, metabolism, and colonic catabolism

Data obtained with in vitro fecal incubations and a feeding study indicate black tea theaflavin and its galloyl derivatives are not absorbed in detectable amounts in either the upper or lower gastrointestinal tract. The theaflavin skeleton is comparatively resistant to degradation by colonic bacteria with a 67% recovery being obtained after a 24 h incubation, which yielded 21 phenolic and aromatic catabolites. The theaflavin galloyl moiety was removed by the microbiota, and the released gallic acid further transformed to 3-O- and 4-O-methyl gallic acids, pyrogallol-1-sulfate and pyrogallol-2-sulfate, which were excreted in urine in amounts equivalent to 94% of intake. The main urinary product potentially derived from breakdown of the theaflavin skeleton was 3-(4′-hydroxyphenyl)propionic acid. A number of the colonic catabolites originating from gallic acid and theaflavins has been reported to be bioactive in ex vivo and in vitro models with a variety of potential modes of action

The Usefulness of Reconstructed 3D Images in Surgical Planning for Cochlear Implantation in a Malformed Ear with an Abnormal Course of the Facial Nerve

Objectives: It is not unusual for a cochlear implantation (CI) candidate to have some type of ear malformation, in particular an abnormal course of the facial nerve (FN). In this study, we attempted to reconstruct a three-dimensional (3D) image of temporal bone structures with malformation using computed tomography (CI) imaging and examined its usefulness in the surgical planning of CI in a malformed ear. Methods: We prepared 3D images for 6 separate CI cases before surgery. First, we manually colored preoperative CT images using Photoshop CS Extended. We then converted the colored CT images to 3D images using Delta Viewer, freeware for Macintosh. Before surgery, we discussed any problems anticipated based on the 3D images and plans for surgery with those who would be performing the CI. Results: Case 1: The subject was a 3-year-old boy with malformed ossicles, semicircular canal (SC) hypoplasia, internal auditory canal stenosis, and an abnormal course of the FN. 3D image indicated that the stapes were absent, and the FN was more anteriorly displaced, so that it was difficult to perform cochleostomy.The surgical findings were similar to those depicted on the 3D image, so we could insert an electrode based on the preoperative image simulation without complications. Case 2: The subject was a 7-year-old boy with malformed stapes, atresia of the round window, cochlear and SC aplasia, and an abnormal course of the FN with bifurcation. CI was performed with no problems, in the same manner as in Case 1. Conclusion: We were able to successfully depict the structures of the inner ear, ossicles, and FN as 3D images, which are very easy to understand visually and intuitively. These 3D images of the malformed ear are useful in preoperative image simulation and in surgical planning for those performing a CI procedure

Case report: A case of unilateral combined central retinal vein occlusion, incomplete central retinal artery occlusion, and papillitis following a third dose of COVID-19 vaccination

PurposeThe aim of this study was to present a case of severe visual loss due to retinal arteriovenous occlusion and papillitis in one eye following vaccination against coronavirus disease (COVID-19).MethodsA 45-year-old man undergoing treatment for hypertension had severely reduced visual acuity in the right eye 1 day after receiving a third dose of a COVID-19 vaccine manufactured by Moderna. Clinical examination showed that the best-corrected visual acuity in the right eye was counting fingers. Other findings included circumferential retinal hemorrhage, perimacular ischemic color, severe macular edema, and severe optic disc swelling, indicating the presence of central retinal vein occlusion, incomplete central retinal artery occlusion, and papillitis. Based on the possibility of post-vaccination inflammation and/or abnormal immune response, three courses of steroid pulse therapy were administered, and the visual acuity slightly improved to 20/1,000.ResultsThree months after the onset of symptoms, macular edema disappeared; conversely, retinal thinning of the macula and extensive non-perfusion areas mainly on the nasal side were noted.ConclusionThe findings in this case suggest that inflammation and abnormal immune response after receiving a COVID-19 vaccination may lead to combined retinal arteriovenous occlusion and papillitis

Green Tea Epigallocatechin Gallate Exhibits Anticancer Effect in Human Pancreatic Carcinoma Cells via the Inhibition of Both Focal Adhesion Kinase and Insulin-Like Growth Factor-I Receptor

The exact molecular mechanism by which epigallocatechin gallate (EGCG) suppresses human pancreatic cancer cell proliferation is unclear. We show here that EGCG-treated pancreatic cancer cells AsPC-1 and BxPC-3 decrease cell adhesion ability on micro-pattern dots, accompanied by dephosphorylations of both focal adhesion kinase (FAK) and insulin-like growth factor-1 receptor (IGF-1R) whereas retained the activations of mitogen-activated protein kinase and mammalian target of rapamycin. The growth of AsPC-1 and BxPC-3 cells can be significantly suppressed by EGCG treatment alone in a dose-dependent manner. At a dose of 100 μM which completely abolishes activations of FAK and IGF-1R, EGCG suppresses more than 50% of cell proliferation without evidence of apoptosis analyzed by PARP cleavage. Finally, the MEK1/2 inhibitor U0126 enhances growth-suppressive effect of EGCG. Our data suggests that blocking FAK and IGF-1R by EGCG could prove valuable for targeted therapy, which can be used in combination with other therapies, for pancreatic cancer

Bilateral Cochlear Implantation for Children in Nagasaki, Japan

Objectives: The number of patients with bilateral cochlear implant (CI) has gradually increased as patients and/or parents recognize its effectiveness. The purpose of this report is to evaluate the efficacy of 29 bilateral CI out of 169 pediatric CI users, who received auditory-verbal/oral habilitation at our hearing center. Methods: We evaluated the audiological abilities 29 Japanese children with bilateral CIs including wearing threshold, word recognition score, speech discrimination score at 1 m from front speaker (SP), 1 m from second CI side SP, speech discrimination score under the noise (S/N ratio=80 dB sound pressure level [SPL]/70 dB SPL, 10 dB) at 1 m from front SP, word recognition score under the noise (S/N ratio=80 dB SPL/70 dB SPL, 10 dB) at 1 m from front SP. Results: Binaural hearing using bilateral CI is better than first CI in all speech understanding tests. Especially, there were significant differences between the results of first CI and bilateral CI on SDS at 70 dB SPL (P=0.02), SDS at 1 m from second CI side SP at 60 dB SPL (P=0.02), word recognition score (WRS) at 1 m from second CI side SP at 60 dB SPL (P=0.02), speech discrimination score (SDS) at 1 m from front SP under the noise (S/N=80/70; P=0.01) and WRS at 1 m from front SP under the noise (S/N=80/70; P=0.002). At every age, a second CI is very effective. However, the results of under 9 years old were better than of over 9 years old on the mean SDS under the noise (S/N=80/70) on second CI (P=0.04). About use of a hearing aid (HA) in their opposite side of first CI, on the WRS and SDS under the noise, there were significant differences between the group of over 3 years and the group of under 10 months of HA non user before second CI. Conclusion: These results may show important binaural effectiveness such as binaural summation and head shadow effect. Bilateral CI is very useful medical intervention for many children with severe-to-profound hearing loss in Japan as well as elsewhere

What Factors Are Associated with Good Performance in Children with Cochlear Implants? From the Outcome of Various Language Development Tests, Research on Sensory and Communicative Disorders Project in Japan: Nagasaki Experience

ObjectivesWe conducted multi-directional language development tests as a part of the Research on Sensory and Communicative Disorders (RSVD) in Japan. This report discusses findings as well as factors that led to better results in children with severe-profound hearing loss.MethodsWe evaluated multiple language development tests in 33 Japanese children with cochlear implants (32 patients) and hearing aid (1 patient), including 1) Test for question and answer interaction development, 2) Word fluency test, 3) Japanese version of the Peabody picture vocabulary test-revised, 4) The standardized comprehension test of abstract words, 5) The screening test of reading and writing for Japanese primary school children, 6) The syntactic processing test of aphasia, 7) Criterion-referenced testing (CRT) for Japanese language and mathematics, 8) Pervasive development disorders ASJ rating scales, and 9) Raven's colored progressive matrices. Furthermore, we investigated the factors believed to account for the better performances in these tests. The first group, group A, consisted of 14 children with higher scores in all tests than the national average for children with hearing difficulty. The second group, group B, included 19 children that scored below the national average in any of the tests.ResultsOverall, the results show that 76.2% of the scores obtained by the children in these tests exceeded the national average scores of children with hearing difficulty. The children who finished above average on all tests had undergone a longer period of regular habilitation in our rehabilitation center, had their implants earlier in life, were exposed to more auditory verbal/oral communication in their education at affiliated institutions, and were more likely to have been integrated in a regular kindergarten before moving on to elementary school.ConclusionIn this study, we suggest that taking the above four factors into consideration will have an affect on the language development of children with severe-profound hearing loss

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation