Antimicrobial Resistance and Inorganic Nanoparticles

Antibiotics are being less effective, which leads to high mortality in patients with infections and a high cost for the recovery of health, and the projections that are had for the future are not very encouraging which has led to consider antimicrobial resistance as a global health problem and to be the object of study by researchers. Although resistance to antibiotics occurs naturally, its appearance and spread have been increasing rapidly due to the inappropriate use of antibiotics in recent decades. A bacterium becomes resistant due to the transfer of genes encoding antibiotic resistance. Bacteria constantly mutate; therefore, their defense mechanisms mutate, as well. Nanotechnology plays a key role in antimicrobial resistance due to materials modified at the nanometer scale, allowing large numbers of molecules to assemble to have a dynamic interface. These nanomaterials act as carriers, and their design is mainly focused on introducing the temporal and spatial release of the payload of antibiotics. In addition, they generate new antimicrobial modalities for the bacteria, which are not capable of protecting themselves. So, nanoparticles are an adjunct mechanism to improve drug potency by reducing overall antibiotic exposure. These nanostructures can overcome cell barriers and deliver antibiotics to the cytoplasm to inhibit bacteria. This work aims to give a general vision between the antibiotics, the nanoparticles used as carriers, bacteria resistance, and the possible mechanisms that occur between them.

Effect of competitive acoustic environments on speech intelligibility

Excessive noise and reverberation times degrade listening abilities in everyday life environments. This is particularly true for school settings. Most classrooms in Italy are settled in historical buildings that generate competitive acoustic environments. So far, few studies investigated the effect of real acoustics on speech intelligibility and on the spatial release from masking, focusing more on laboratory conditions. Also, the effect of noise on speech intelligibility was widely investigated considering its energetic rather than its informational content. Therefore, a study involving normal hearing adults was performed presenting listening tests via headphone and considering the competitive real acoustics of two primary-school classrooms with reverberation time of 0.4 s and 3.1 s, respectively. The main objective was the investigation of the effect of reverberation and noise on the spatial release from masking to help the design of learning environments. Binaural room impulse responses were acquired, with noise sources at different azimuths from the listener’s head. The spatial release from masking was significantly affected by noise type and reverberation. Longer reverberation times brought to worst speech intelligibility, with speech recognition thresholds higher by 6 dB on average. Noise with an informational content was detrimental by 7 dB with respect to an energetic noise.

Impacts of Diabetes, Aging, and Hearing Loss on Speech-on-Speech Masking and Spatial Release in a Large Veteran Cohort

Purpose Type 2 diabetes mellitus (DM2) is associated with impaired hearing. However, the evidence is less clear if DM2 can lead to difficulty understanding speech in complex acoustic environments, independently of age and hearing loss effects. The purpose of this study was to estimate the magnitude of DM2-related effects on speech understanding in the presence of competing speech after adjusting for age and hearing. Method A cross-sectional study design was used to investigate the relationship between DM2 and speech understanding in 190 Veterans ( M age = 47 years, range: 25–76). Participants were classified as having no diabetes ( n = 74), prediabetes ( n = 19), or DM2 that was well controlled ( n = 24) or poorly controlled ( n = 73). A test of spatial release from masking (SRM) was presented in a virtual acoustical simulation over insert earphones with multiple talkers using sentences from the coordinate response measure corpus to determine the target-to-masker ratio (TMR) required for 50% correct identification of target speech. A linear mixed model of the TMR results was used to estimate SRM and separate effects of diabetes group, age, and low-frequency pure-tone average (PTA-low) and high-frequency pure-tone average. A separate model estimated the effects of DM2 on PTA-low. Results After adjusting for hearing and age, diabetes-related effects remained among those whose DM2 was well controlled, showing an SRM loss of approximately 0.5 dB. Results also showed effects of hearing loss and age, consistent with the literature on people without DM2. Low-frequency hearing loss was greater among those with DM2. Conclusions In a large cohort of Veterans, low-frequency hearing loss and older age negatively impact speech understanding. Compared with nondiabetics, individuals with controlled DM2 have additional auditory deficits beyond those associated with hearing loss or aging. These results provide a potential explanation for why individuals who have diabetes and/or are older often report difficulty understanding speech in real-world listening environments. Supplemental Material https://doi.org/10.23641/asha.16746475

Angiocrine IGFBP3 Spatially Coordinates IGF Signaling During Neonatal Cardiac Regeneration

To identify non cellautonomous effectors of cardiomyocyte mitosis, we analyzed a transcriptomic screen of regenerating and non regenerating neonatal hearts for differentially expressed secreted proteins, which we hypothesized could include candidate mitogens. We identified and validated IGFBP3, which has a Janus-like stabilizing and sequestering effect on IGF growth factors, as a neonatal injury associated secreted protein. IGFBP3 is expressed by and secreted from vascular cells in the neonatal heart after cardiac injury, notably in the infarct border zone. We found that global deletion of IGFBP3 blunted neonatal regeneration, while gain of function experiments using recombinant IGFBP3 and a transgenic mouse model uncovered a pro mitotic effect of IGFBP3 on cardiomyocytes in vitro and in the adult heart. We show that site specific expression of an IGFBP3 protease (PAPPA2) and its inhibitor (STC2) coordinate the spatial release of IGF2 in the infarct zone to regio selectively activate the INSR/ERK/AKT cell growth pathways in cardiomyocytes. Collectively, our work highlights the spatiotemporal orchestration of endothelial cardiomyocyte interactions that are required for neonatal cardiac regeneration.

Bimodal Fitting and Bilateral Cochlear Implants in Children With Significant Residual Hearing: The Impact of Asymmetry in Spatial Release of Masking on Localization

Purpose This study aimed to gain more insight into the primary auditory abilities of children with significant residual hearing in order to improve decision making when choosing between bimodal fitting or sequential bilateral cochlear implantation. Method Sound localization abilities, spatial release of masking, and fundamental frequency perception were tested. Nine children with bimodal fitting and seven children with sequential bilateral cochlear implants were included in the study. As a reference, 15 children with normal hearing and two children with simultaneous bilateral cochlear implants were included. Results On all outcome measures, the implanted children performed worse than the normal hearing children. For high-frequency localization, children with sequential bilateral cochlear implants performed significantly better than children with bimodal fitting. Compared to children with normal hearing, the left–right asymmetry in spatial release of masking was significant. When the implant was hindered by noise, bimodally fitted children obtained significantly lower spatial release of masking compared to when the hearing aid was hindered by noise. Overall, the larger the left–right asymmetry in spatial release of masking, the poorer the localization skills. No significant differences were found in fundamental frequency perception between the implant groups. Conclusions The data hint to an advantage of bilateral implantation over bimodal fitting. The extent of asymmetry in spatial release of masking is a promising tool for decision making when choosing whether to continue with the hearing aid or to provide a second cochlear implant in children with significant residual hearing.