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n3-PUFA impact health in several ways, including cardiovascular protection and anti-inflammatory effects, but the underlying mechanisms are not fully understood. In this exploratory study involving 31 healthy subjects, we aimed to investigate the effects of 12 weeks of fish-oil supplementation (1500 mg EPA+DHA/day) on the physical properties of multiple blood cell types. We used deformability cytometry (DC) for all cell types and Laser-assisted Optical Rotational Red Cell Analysis (Lorrca) to assess red blood cell (RBC) deformability. We also investigated the correlation between changes in the physical properties of blood cells and changes in the Omega-3 Index (O3I), defined as the relative content of EPA+DHA in RBCs. Following supplementation, the mean±SD O3I increased from 5.3 %±1.5 % to 8.3 %±1.4 % (p < 0.001). No significant changes in RBC properties were found by both techniques. However, by DC we observed a consistent pattern of physical changes in lymphocytes, neutrophils and monocytes. Among these were significant increases in metrics correlated with the cells' deformability resulting in less stiff cells. The results suggest that leukocytes become softer and have an increased ability to deform under induced short-term physical stress such as hydrodynamic force in the circulation. These changes could impact immune function since softer leukocytes can potentially circulate more easily and could facilitate a more rapid response to systemic inflammation or infection. In conclusion, fish-oil supplementation modulates some physical properties of leukocyte-subfractions, potentially enhancing their biological function. Further studies are warranted to explore the impact of n3-PUFA on blood cell biology, particularly in disease states associated with leukocyte dysregulation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Primary lymphedema is caused by developmental and functional defects of the lymphatic vascular system that result in accumulation of protein-rich fluid in tissues, resulting in edema. The 28 currently known genes causing primary lymphedema can explain <30% of cases. Angiopoietin 1 (ANGPT1) and ANGPT2 function via the TIE1-TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and 2) receptor complex and α5β1 integrin to form an endothelial cell signaling pathway that is critical for blood and lymphatic vessel formation and remodeling during embryonic development, as well as for homeostasis of the mature vasculature. By screening a cohort of 543 individuals affected by primary lymphedema, we identified one heterozygous de novo ANGPT2 whole-gene deletion and four heterozygous ANGPT2 missense mutations. Functional analyses revealed three missense mutations that resulted in decreased ANGPT2 secretion and inhibited the secretion of wild-type (WT)-ANGPT2, suggesting that they have a dominant-negative effect on ANGPT2 signaling. WT-ANGPT2 and soluble mutants T299M and N304K activated TIE1 and TIE2 in an autocrine assay in human lymphatic endothelial cells. Molecular modeling and biophysical studies showed that amino-terminally truncated ANGPT subunits formed asymmetrical homodimers that bound TIE2 in a 2:1 ratio. The T299M mutant, located in the dimerization interphase, showed reduced integrin α5 binding, and its expression in mouse skin promoted hyperplasia and dilation of cutaneous lymphatic vessels. These results demonstrate that primary lymphedema can be associated with ANGPT2 mutations and provide insights into TIE1 and TIE2 activation mechanisms., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To investigate the safety and efficacy of a new bone conduction hearing implant in children, during a 3-month follow-up period., Study Design: Prospective, single-subject repeated-measures design in which each subject serves as his/her own control., Setting: Otolaryngology departments of four Austrian hospitals., Patients: Twelve German-speaking children aged 5 to 17 suffering from conductive or mixed hearing loss, with an upper bone conduction threshold limit of 45 dB HL at frequencies between 500 and 4000 Hz., Intervention: Implantation of the Bonebridge transcutaneous bone conduction hearing implant (tBCI)., Main Outcome Measures: The subjects' audiometric thresholds (air conduction, bone conduction, and sound field at frequencies 500 Hz to 8 kHz) and speech perception (word recognition scores [WRS] and 50% word intelligibility in sentences [SRT50%]) were tested preoperatively and at 1 and 3 months postoperatively. The patients were also monitored for adverse events and they or their parents filled out questionnaires to analyze satisfaction levels., Results: Speech perception as measured by WRS and SRT50% improved on average approximately 67.6% and 27.5 dB, respectively, 3 months after implantation. Aided thresholds also improved postoperatively, showing statistical significance at all tested frequencies. Air conduction and bone conduction thresholds showed no significant changes, confirming that subjects' residual unaided hearing was not damaged by the treatment. Only minor adverse events were reported and resolved by the end of the study., Conclusion: Safety and efficacy of the new bone conduction implant was demonstrated in children followed up to 3 months postoperatively.

Lymphedema is caused by dysfunction of lymphatic vessels, leading to disabling swelling that occurs mostly on the extremities. Lymphedema can be either primary (congenital) or secondary (acquired). Familial primary lymphedema commonly segregates in an autosomal dominant or recessive manner. It can also occur in combination with other clinical features. Nine mutated genes have been identified in different isolated or syndromic forms of lymphedema. However, the prevalence of primary lymphedema that can be explained by these genetic alterations is unknown. In this study, we investigated 7 of these putative genes. We screened 78 index patients from families with inherited lymphedema for mutations in FLT4, GJC2, FOXC2, SOX18, GATA2, CCBE1, and PTPN14. Altogether, we discovered 28 mutations explaining 36% of the cases. Additionally, 149 patients with sporadic primary lymphedema were screened for FLT4, FOXC2, SOX18, CCBE1, and PTPN14. Twelve mutations were found that explain 8% of the cases. Still unidentified is the genetic cause of primary lymphedema in 64% of patients with a family history and 92% of sporadic cases. Identification of those genes is important for understanding of etiopathogenesis, stratification of treatments and generation of disease models. Interestingly, most of the proteins that are encoded by the genes mutated in primary lymphedema seem to act in a single functional pathway involving VEGFR3 signaling. This underscores the important role this pathway plays in lymphatic development and function and suggests that the unknown genes also have a role.

Conclusions: The round window (RW) approach in the use of the Vibrant Soundbridge(®) (VSB) is a safe and effective treatment of conductive and mixed hearing losses for a period of more than 3 years of device use., Objective: To investigate the long-term safety and efficacy as well as user satisfaction of patients with conductive and mixed hearing losses implanted with the VSB using RW vibroplasty., Methods: Twelve patients with conductive and mixed hearing losses were evaluated after 40 months of daily VSB use. Safety was assessed by evaluating reports of postoperative medical and surgical complications as well as by changes in bone conduction hearing thresholds. Efficacy outcome measures included aided and unaided hearing thresholds, speech recognition in quiet and in noise and subjective benefit questionnaires., Results: The safety results revealed no significant medical complications. One subject experienced sudden hearing loss after 18-24 months of device use, but still continues to wear the device to her satisfaction. With regard to efficacy, there were no significant changes from short- to long-term results in aided word understanding, functional gain or speech recognition threshold, suggesting that the outcomes are stable over time. Subjective questionnaires revealed either the same or better results compared with the short-term data.

Background/aims: The Vibrant Soundbridge (VSB) is an active middle ear implant, 'direct-drive' hearing system for the treatment of hearing loss. Recently, the VSB has been applied to conductive and mixed hearing losses. The aim of this study is to evaluate aided benefit, speech recognition in quiet and noise, subjective benefits, changes in residual hearing, and medical and surgical complications in adults with conductive or mixed hearing losses implanted with the VSB using Round Window (RW) Vibroplasty., Methods: Twelve German-speaking adults participated in a single-subject, repeated measures study design comparing their performance using the VSB with their own unaided preoperative performance. Hearing performance and changes in residual hearing were assessed using routine audiometric measures, sound field thresholds, and word and sentence recognition in quiet and in noise. Subjective benefits, including subjective hearing performance, device satisfaction, and quality of life were evaluated using the Abbreviated Profile of Hearing Aid Benefit, the Hearing Device Satisfaction Scale, and the Glasgow Benefit Inventory, respectively., Results: Aided hearing thresholds, word recognition at conversational levels, and sentence recognition in quiet and noise were significantly improved without significant changes in residual cochlear hearing and without major medical and surgical complications. One subject required repositioning surgery to improve transducer coupling with the RW membrane. Subjective benefit and device satisfaction were good, as were overall and general quality of life., Conclusion: The VSB, implanted using RW vibroplasty, is a safe and effective treatment for adults with conductive and mixed hearing losses who may have few, if any, other options., (Copyright (c) 2010 S. Karger AG, Basel.)

Background/aims: To evaluate gain at threshold level and speech recognition performance of 54 subjects with mild-to-severe symmetrical sensorineural hearing loss (SNHL) that received the active middle ear implant system Vibrant Soundbridge (VSB)., Methods: Pre- and postoperative assessments of hearing thresholds and monosyllabic word discrimination were performed in a homogeneous group of 54 adults who received a VSB system (VORP 502/AP 404) in an active middle ear implant (AMEI) program in a tertiary referral hospital. All subjects included in this study had mild-to-severe, predominately sloping SNHL. Gain at threshold level and speech recognition results were assessed for unaided and aided conditions using the patient's walk-in hearing aid (HA) and the VSB in a retrospective study design., Results: A comparison of pre- and postoperative unaided air conduction thresholds revealed a mean decrease in pure tone averages of 3.9 dB (0.25-8 kHz). Gain at threshold level (unaided thresholds minus AMEI-aided thresholds) was, on average, 20.9 dB at 0.5 kHz, 20.5 dB at 1 kHz, 23.8 dB at 2 kHz, 30.2 dB at 3 kHz, 36.1 dB at 4 kHz, 37.6 dB at 6 kHz and 37.9 dB at 8 kHz. Monosyllabic word discrimination at 65 dB SPL improved from a mean of 30% in the unaided condition to 44% for the HA-aided condition (p<0.05), with a further increase to 57% for the VSB-aided condition (p<0.05, compared to the HA)., Conclusion: The AMEI system VSB can be considered as an effective rehabilitation alternative in subjects with mild-to-severe SNHL and unsatisfying benefit from conventional hearing aids., (Copyright (c) 2010 S. Karger AG, Basel.)