Effects of retro-nasal aroma release on satiation

It is suggested that the brain response of a food odour sensed retro-nasally is related to satiation. The extent of retro-nasal aroma release during consumption depends on the physical structure of a food, i.e. solid foods generate a longer, more pronounced retro-nasal aroma release than liquid foods. The aim of this study was to investigate if a beverage becomes more satiating when the retro-nasal aroma release profile coincides with the profile of a (soft) solid food. In a double-blind placebo-controlled randomised cross-over full factorial design, twenty-seven healthy subjects (fourteen males and thirteen females; aged 16-65 years; BMI 19-37 kg/m(2) were administered aroma profiles by a computer-controlled stimulator based on air dilution olfactometry. Profile A consisted of a profile that is obtained during consumption of normal beverages. Profile B is normally observed during consumption of (soft) solids. The two profiles were produced with strawberry aroma and administered in a retro-nasal fashion, while the subjects consumed a sweetened milk drink. Before, during and after the sensory stimulation, appetite profile measurements were performed. Subjects felt significantly more satiated if they were aroma stimulated with profile B (P = 0.04). After stimulation with sweet strawberry aroma, there was a significant decrease in desire to eat sweet products (P = 0.0001). In conclusion, perceived satiation was increased by altering the extent of retro-nasal aroma release

ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab

The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance. Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation. However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive. Here, we demonstrate that ErbB2 is modified with both alpha 2,6- and alpha 2,3-sialylated glycan structures in GC clinical specimens. In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain. Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs. Overall, our data demonstrates that ST6Gal1-mediated aberrant alpha 2,6-sialylation actively tunes the resistance of ErbB2-driven GC cells to trastuzumab.Proteomic

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Suboccipital neuropathy after bone conduction device placement

Item does not contain fulltextOBJECTIVE: To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery. DESCRIPTION: A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed chronic pain at the implantation site. The pain led to minimal neck movement, which resulted in complaints of the shoulder and arm on the left side. She was treated by an orthopaedic surgeon for a frozen shoulder. Pain medication and occipital nerve blocking had no sustained effect on the pain. DISCUSSION: Occipital neuropathy is a syndrome with continuous aching involving the occipital and parietal scalp caused by trauma or peripheral compression of the occipital nerves. The most common causes of occipital neuropathy are probably direct trauma to the nerve and hypertrophic fibrosis of subcutaneous tissue surrounding the nerve. Scar formation after surgery may therefore cause entrapment of the nerve. CONCLUSION: We describe a case of occipital neuropathy as a complication of BAHA surgery

Suboccipital neuropathy after bone conduction device placement

OBJECTIVE: To describe the clinical characteristics of a 70-year-old female with occipital neuropathy following bone conduction device surgery. DESCRIPTION: A 65-year-old woman underwent bone conduction device placement surgery on the left temporal bone. Postoperatively she progressively developed chronic pain at the implantation site. The pain led to minimal neck movement, which resulted in complaints of the shoulder and arm on the left side. She was treated by an orthopaedic surgeon for a frozen shoulder. Pain medication and occipital nerve blocking had no sustained effect on the pain. DISCUSSION: Occipital neuropathy is a syndrome with continuous aching involving the occipital and parietal scalp caused by trauma or peripheral compression of the occipital nerves. The most common causes of occipital neuropathy are probably direct trauma to the nerve and hypertrophic fibrosis of subcutaneous tissue surrounding the nerve. Scar formation after surgery may therefore cause entrapment of the nerve. CONCLUSION: We describe a case of occipital neuropathy as a complication of BAHA surgery

Toepassen van Fysica Zinvol bij het Horen : Een Nieuw Gehoorparadigma

Based on our insights derived from literature we arrive at two more basic principles that form the cornerstones of our model: namely, the fact that the attenuation of the eardrum and the ossicular chain are at the root of the extremely large dynamic range of our auditory sense, and the fact that the bone conduction phenomenon is actually the result of the push-pull movement of the perilymph fluid instead of the presumed deformation of the bony structures. These three main premises form the basis for this new paradigm of the human auditory sense