The mean resonance frequency of the human middle ear under air conduction (AC) excitation is known to be around 0.8-1.2 kHz. However, studies suggest that the mean resonance frequency under bone conduction (BC) excitation is at a higher frequency around 1.5-2 kHz. To identify the cause for this difference, middle-ear responses to both AC and BC excitations were measured at the umbo and lateral process of the malleus using five human cadaver temporal bones. The resonance modes identified from these measurements, along with finite element analysis results, indicate the presence of two ossicular modes below 2 kHz. The dominant mode under AC excitation is the first mode, which typically occurs around 1.2 kHz and is characterized by a "hinging" ossicular motion, whereas the dominant mode under BC excitation is the second mode, which typically occurs around 1.7 kHz and is characterized by a "pivoting" ossicular motion. The results indicate that this second mode is responsible for the translational component in the malleus handle motion. The finding is also consistent with the hypothesis that a middle-ear structural resonance is responsible for the prominent peak seen at 1.5-2 kHz in BC limit data.

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In extremely loud noise environments, it is important to not only protect one’s hearing against noise transmitted through the air-conduction (AC) pathway, but also through the bone-conduction (BC) pathways. Much of the energy transmitted through the BC pathways is concentrated in the mid-frequency range around 1.5–2 kHz, which is likely due to the structural resonance of the middle ear. One potential approach for mitigating this mid-frequency BC noise transmission is to introduce a positive or negative static pressure in the ear canal, which is known to reduce BC as well as AC hearing sensitivity. In the present study, middle-ear ossicular velocities at the umbo and stapes were measured using human cadaver temporal bones in response to both BC and AC excitations, while static air pressures of ±400 mm H2O were applied in the ear canal. For the maximum negative pressure of −400 mm H2O, mean BC stapes-velocity reductions of about 5–8 dB were observed in the frequency range from 0.8 to 2.5 kHz, with a peak reduction of 8.6(± 4.7) dB at 1.6 kHz. Finite-element analysis indicates that the peak BC-response reduction tends to be in the mid-frequency range because the middle-ear BC resonance, which is typically around 1.5–2 kHz, is suppressed by the pressure-induced stiffening of the middle-ear structure. The measured data also show that the BC responses are reduced more for negative static pressures than for positive static pressures. This may be attributable to a difference in the distribution of the stiffening among the middle-ear components depending on the polarity of the static pressure. The characteristics of the BC-response reductions are found to be largely consistent with the available psychoacoustic data, and are therefore indicative of the relative importance of the middle-ear mechanism in BC hearing.

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Objective: Cardiovascular disease, a major cause of mortality and morbidity, exhibits sexual dimorphism since the onset of cardiovascular disease occurs later in women than in men. The loss of cardioprotection in older women may be due to an increase in arterial stiffness after menopause. Free fatty acid metabolites of polyunsaturated fatty acids, called oxylipins, are known to impact vessel function and may be responsible for the vascular benefits of polyunsaturated fatty acids. The objectives of this study were to compare the plasma oxylipin profiles of young females (20–55 years), older females (55 + ), and older males (55 + ) and to identify associations between oxylipins and cardiovascular disease risk factors, such as obesity and arterial stiffness. Approach and Results: We quantified plasma oxylipins by high-performance liquid chromatography–tandem mass spectrometry in archived samples taken from completed clinical trials. We identified 3 major 12-lipoxygenase products, 12-hydroxy-eicosatetraenoic acid, 12-hydroxy-eicosapentaenoic acid, and 14-hydroxy-docosahexaenoic acid, that are present at high levels in young females compared with older females and males. These oxylipins also decreased with obesity and displayed robust negative associations with arterial stiffness as assessed by brachial-ankle pulse wave velocity. According to multiple linear regression modeling, these associations were maintained even after correcting for body mass index category combined with either age, menopausal status, or estradiol levels. Using linear discriminant analysis, the combination of these 3 oxylipins effectively distinguished participants according to both brachial-ankle pulse wave velocity risk group and age. Conclusions: Higher 12-lipoxygenase oxylipin plasma concentrations associated with lower arterial stiffness in premenopausal females may be an important contributing factor to sex differences in cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT01661543, NCT01562171, NCT01890330, NCT02571114 and NCT02317588.

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Increased production of long-chain unsaturated fatty acids (LCUFA) can have a positive effect on the nutritional value of ruminant milk for human consumption. In nonruminant species, fatty acid elongase 5 (ELOVL5) is a key enzyme for endogenous synthesis of long-chain unsaturated fatty acids. However, whether ELOVL5 protein plays a role (if any) in ruminant mammary tissue remains unclear. In the present study, we assessed the mRNA abundance of ELOVL5 at 3 stages of lactation in goat mammary tissue. Results revealed that ELOVL5 had the lowest expression at peak lactation compared with the nonlactating and late-lactating periods. The ELOVL5 was overexpressed or knocked down to assess its role in goat mammary epithelial cells. Results revealed that ELOVL5 overexpression increased the expression of perilipin2 (PLIN2) and decreased diacylglycerolacyltransferase 2 (DGAT2) and fatty acid desaturase 2 (FADS2) mRNA, but had no effect on the expression of DGAT1, FADS1, and stearoyl-CoA desaturase 1 (SCD1). Overexpression of ELOVL5 decreased the concentration of C16:1n-7, whereas no significant change in C18:1n-7 and C18:1n-9 was observed. Knockdown of ELOVL5 decreased the expression of PLIN2 but had no effect on DGAT1, DGAT2, FADS1, FADS2, and SCD1 mRNA expression. Knockdown of ELOVL5 increased the concentration of C16:1n-7 and decreased that of C18:1n-7. The alterations of expression of genes related to lipid metabolism after overexpression or knockdown of ELOVL5 suggested a negative feedback regulation by the products of ELOVL5 activation. However, the content of triacylglycerol was not altered by knockdown or overexpression of ELOVL5 in goat mammary epithelial cells, which might have been due to the insufficient availability of substrate in vitro. Collectively, these are the first in vitro results highlighting an important role of ELOVL5 in the elongation of 16-carbon to 18-carbon unsaturated fatty acids in ruminant mammary cells.