Cortical cross-modal re-organization, or recruitment of auditory cortical areas for visual processing, has been well-documented in deafness. However, the degree of sensory deprivation necessary to ...induce such cortical plasticity remains unclear. We recorded visual evoked potentials (VEP) using high-density electroencephalography in nine persons with adult-onset mild-moderate hearing loss and eight normal hearing control subjects. Behavioral auditory performance was quantified using a clinical measure of speech perception-in-noise. Relative to normal hearing controls, adults with hearing loss showed significantly larger P1, N1, and P2 VEP amplitudes, decreased N1 latency, and a novel positive component (P2') following the P2 VEP. Current source density reconstruction of VEPs revealed a shift toward ventral stream processing including activation of auditory temporal cortex in hearing-impaired adults. The hearing loss group showed worse than normal speech perception performance in noise, which was strongly correlated with a decrease in the N1 VEP latency. Overall, our findings provide the first evidence that visual cross-modal re-organization not only begins in the early stages of hearing impairment, but may also be an important factor in determining behavioral outcomes for listeners with hearing loss, a finding which demands further investigation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Age-related hearing loss (ARHL) is associated with cognitive decline as well as structural and functional brain changes. However, the mechanisms underlying neurocognitive deficits in ARHL are poorly ...understood and it is unclear whether clinical treatment with hearing aids may modify neurocognitive outcomes. To address these topics, cortical visual evoked potentials (CVEPs), cognitive function, and speech perception abilities were measured in 28 adults with untreated, mild-moderate ARHL and 13 age-matched normal hearing (NH) controls. The group of adults with ARHL were then fit with bilateral hearing aids and re-evaluated after 6 months of amplification use. At baseline, the ARHL group exhibited more extensive recruitment of auditory, frontal, and pre-frontal cortices during a visual motion processing task, providing evidence of cross-modal re-organization and compensatory cortical neuroplasticity. Further, more extensive cross-modal recruitment of the right auditory cortex was associated with greater degree of hearing loss, poorer speech perception in noise, and worse cognitive function. Following clinical treatment with hearing aids, a reversal in cross-modal re-organization of auditory cortex by vision was observed in the ARHL group, coinciding with gains in speech perception and cognitive performance. Thus, beyond the known benefits of hearing aid use on communication, outcomes from this study provide evidence that clinical intervention with well-fit amplification may promote more typical cortical organization and functioning and provide cognitive benefit.
Visual cross-modal re-organization is a neurophysiological process that occurs in deafness. The intact sensory modality of vision recruits cortical areas from the deprived sensory modality of ...audition. Such compensatory plasticity is documented in deaf adults and animals, and is related to deficits in speech perception performance in cochlear-implanted adults. However, it is unclear whether visual cross-modal re-organization takes place in cochlear-implanted children and whether it may be a source of variability contributing to speech and language outcomes. Thus, the aim of this study was to determine if visual cross-modal re-organization occurs in cochlear-implanted children, and whether it is related to deficits in speech perception performance.
Visual evoked potentials (VEPs) were recorded via high-density EEG in 41 normal hearing children and 14 cochlear-implanted children, aged 5-15 years, in response to apparent motion and form change. Comparisons of VEP amplitude and latency, as well as source localization results, were conducted between the groups in order to view evidence of visual cross-modal re-organization. Finally, speech perception in background noise performance was correlated to the visual response in the implanted children.
Distinct VEP morphological patterns were observed in both the normal hearing and cochlear-implanted children. However, the cochlear-implanted children demonstrated larger VEP amplitudes and earlier latency, concurrent with activation of right temporal cortex including auditory regions, suggestive of visual cross-modal re-organization. The VEP N1 latency was negatively related to speech perception in background noise for children with cochlear implants.
Our results are among the first to describe cross modal re-organization of auditory cortex by the visual modality in deaf children fitted with cochlear implants. Our findings suggest that, as a group, children with cochlear implants show evidence of visual cross-modal recruitment, which may be a contributing source of variability in speech perception outcomes with their implant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SARS‐CoV‐2 and other respiratory viruses spread via aerosols generated by infected people. Face masks can limit transmission. However, widespread use of disposable masks consumes tremendous resources ...and generates waste. Here, a novel material for treating blown polypropylene filtration media used in medical‐grade masks to impart antimicrobial activity is reported. To produce thin copper@ZIF‐8 core‐shell nanowires (Cu@ZIF‐8 NWs), Cu NWs are stabilized using a pluronic F‐127 block copolymer, followed by growth of ZIF‐8 to obtain uniform core‐shell structures. The Cu@ZIF‐8 NWs are applied to filtration media by dip coating. Aerosol filtration efficiency decreases upon exposure to ethanol (solvent for dip‐coating), but increases with addition of Cu@ZIF‐8 NWs. Cu@ZIF‐8 NWs shows enhanced antibacterial activity, compared to Cu NWs or ZIF‐8 alone, against Streptococcus mutans and Escherichia coli. Antiviral activity against SARS‐CoV‐2 is assayed using virus‐infected Vero E6 cells, demonstrating 55% inhibition of virus replication after 48 h by 1 µg of Cu@ZIF‐8 NWs per well. Cu@ZIF‐8 NWs’ cytotoxicity is tested against four cell lines, and their effect on inflammatory response in A549 cells is examined, demonstrating good biocompatibility. This low‐cost, scalable synthesis and straightforward deposition of Cu@ZIF‐8 NWs onto filter media has great potential to reduce disease transmission, resource consumption, and environmental impact of waste.
Antimicrobial copper nanowires coated with ZIF‐8 metal organic framework (Cu@ZIF‐8 NWs) are prepared and applied to blown polypropylene filter media typically used in face masks. The Cu@ZIF‐8 NWs and treated mask material show enhanced antimicrobial activity that can enable their use in self‐sanitizing reusable face masks and other medical textiles to reduce transmission of disease, including COVID‐19.
Under conditions of profound sensory deprivation, the brain has the propensity to reorganize. For example, intact sensory modalities often recruit deficient modalities' cortices for neural ...processing. This process is known as cross-modal reorganization and has been shown in congenitally and profoundly deaf patients. However, much less is known about cross-modal cortical reorganization in persons with less severe cases of age-related hearing loss (ARHL), even though such cases are far more common. Thus, we investigated cross-modal reorganization between the auditory and somatosensory modalities in older adults with normal hearing (NH) and mild-moderate ARHL in response to vibrotactile stimulation using high density electroencephalography (EEG). Results showed activation of the somatosensory cortices in adults with NH as well as those with hearing loss (HL). However, adults with mild-moderate ARHL also showed robust activation of auditory cortical regions in response to somatosensory stimulation. Neurophysiologic data exhibited significant correlations with speech perception in noise outcomes suggesting that the degree of cross-modal reorganization may be associated with functional performance. Our study presents the first evidence of somatosensory cross-modal reorganization of the auditory cortex in adults with early-stage, mild-moderate ARHL. Our findings suggest that even mild levels of ARHL associated with communication difficulty result in fundamental cortical changes.
Immune checkpoint therapy (ICT) has transformed cancer treatment in recent years; however, treatment response is not uniform across tumor types. The tumor immune microenvironment plays a critical ...role in determining response to ICT; therefore, understanding the differential immune infiltration between ICT-sensitive and ICT-resistant tumor types will help to develop effective treatment strategies. We performed a comprehensive analysis of the immune tumor microenvironment of an ICT-sensitive tumor (melanoma, n = 44) and an ICT-resistant tumor (pancreatic cancer, n = 67). We found that a pancreatic tumor has minimal tomoderate infiltration of CD3, CD4, and CD8 T cells; however, the immune infiltrates are predominantly present in the stromal area of the tumor and are excluded from tumoral area compared with melanoma, where the immune infiltrates are primarily present in the tumoral area. Metastatic pancreatic ductal adenocarcinomas (PDACs) had a lower infiltration of total T cells compared with resectable primary PDACs, suggesting that metastatic PDACs have poor immunogenicity. Further, a significantly higher number of CD68⁺ macrophages and VISTA⁺ cells (also known as V-domain immunoglobulin suppressor of T cell activation) were found in the pancreatic stromal area compared with melanoma. We identified VISTA as a potent inhibitory checkpoint that is predominantly expressed on CD68+ macrophages on PDACs. These data suggest that VISTA may be a relevant immunotherapy target for effective treatment of patients with pancreatic cancer.
Deprived of sensory input, as in deafness, the brain tends to reorganize. Cross-modal reorganization occurs when cortices associated with deficient sensory modalities are recruited by other, intact ...senses for processing of the latter's sensory input. Studies have shown that this type of reorganization may affect outcomes when sensory stimulation is later introduced via intervention devices. One such device is the cochlear implant (CI). Hundreds of thousands of CIs have been fitted on people with hearing impairment worldwide, many of them children. Factors such as age of implantation have proven useful in predicting speech perception outcome with these devices in children. However, a portion of the variance in speech understanding ability remains unexplained. It is possible that the degree of cross-modal reorganization may explain additional variability in listening outcomes. Thus, the current study aimed to examine possible somatosensory cross-modal reorganization of the auditory cortices. To this end we used high density EEG to record cortical responses to vibrotactile stimuli in children with normal hearing (NH) and those with CIs. We first investigated cortical somatosensory evoked potentials (CSEP) in NH children, in order to establish normal patterns of CSEP waveform morphology and sources of cortical activity. We then compared CSEP waveforms and estimations of cortical sources between NH children and those with CIs to assess the degree of somatosensory cross-modal reorganization. Results showed that NH children showed expected patterns of CSEP and current density reconstructions, such that postcentral cortices were activated contralaterally to the side of stimulation. Participants with CIs also showed this pattern of activity. However, in addition, they showed activation of auditory cortical areas in response to somatosensory stimulation. Additionally, certain CSEP waveform components were significantly earlier in the CI group than the children with NH. These results are taken as evidence of cross-modal reorganization by the somatosensory modality in children with CIs. Speech perception in noise scores were negatively associated with CSEP waveform components latencies in the CI group, suggesting that the degree of cross-modal reorganization is related to speech perception outcomes. These findings may have implications for clinical rehabilitation in children with cochlear implants.
Of all the numerous nanosized extracellular vesicles released by a cell, the endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, ...low immunogenicity, and targeted delivery capabilities. This review critically evaluates the transformative potential of exosome-based modalities across pharmaceutical and precision medicine landscapes. Because of their precise targeted biomolecular cargo delivery, exosomes are posited as ideal candidates in drug delivery, enhancing regenerative medicine strategies, and advancing diagnostic technologies. Despite the significant market growth projections of exosome therapy, its utilization is encumbered by substantial scientific and regulatory challenges. These include the lack of universally accepted protocols for exosome isolation and the complexities associated with navigating the regulatory environment, particularly the guidelines set forth by the U.S. Food and Drug Administration (FDA). This review presents a comprehensive overview of current research trajectories aimed at addressing these impediments and discusses prospective advancements that could substantiate the clinical translation of exosomal therapies. By providing a comprehensive analysis of both the capabilities and hurdles inherent to exosome therapeutic applications, this article aims to inform and direct future research paradigms, thereby fostering the integration of exosomal systems into mainstream clinical practice.
Aims/hypothesis
Shift-work is associated with circadian rhythm disruption and an increased risk of obesity and type 2 diabetes. We sought to determine the effect of rotational shift-work on glucose ...metabolism in humans.
Methods
We studied 12 otherwise healthy nurses performing rotational shift-work using a randomised crossover study design. On each occasion, participants underwent an isotope-labelled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model. We sought to determine differences in fasting and postprandial glucose metabolism during the day shift vs the night shift.
Results
Postprandial glycaemic excursion was higher during the night shift (381±33 vs 580±48 mmol/l per 5 h,
p
<0.01). The time to peak insulin and C-peptide and nadir glucagon suppression in response to meal ingestion was also delayed during the night shift. While insulin action did not differ between study days, the beta cell responsivity to glucose (59±5 vs 44±4 × 10
−9
min
−1
;
p
<0.001) and disposition index were decreased during the night shift.
Conclusions/interpretation
Impaired beta cell function during the night shift may result from normal circadian variation, the effect of rotational shift-work or a combination of both. As a consequence, higher postprandial glucose concentrations are observed during the night shift.
Over the last decade in the United States (US), the burden of chronic disease, health care costs, and fragmented care delivery have increased at alarming rates. To address these challenges, ...policymakers have prioritized new payment and delivery models to incentivize better integrated health and social services.
This paper outlines three major national and state policy initiatives to improve integrated health and social care over the last ten years in the US, with a focus on the Medicaid public insurance program for Americans with low incomes. Activities supported by these initiatives include screening patients for social risks in primary care clinics; building new cross-sector collaborations; financing social care with healthcare dollars; and sharing data across health, social and community services. Stakeholders from the private sector, including health systems and insurers, have partnered to advance and scale these initiatives. This paper describes the implementation and effectiveness of such efforts, and lessons learned from translating policy to practice.
National policies have catalyzed initiatives to test new integrated health and social care models, with the ultimate goal of improving population health and decreasing costs. Preliminary findings demonstrated the need for validated measures of social risk, engagement across levels of organizational leadership and frontline staff, and greater flexibility from national policymakers in order to align incentives across sectors.
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