Achromatic complex holograms for laser mode conversion.

While conventional complex phase masks are chromatic, we present an achromatic holographic phase mask capable of performing optical beam transformations in a spectral range exceeding 1000 nm. The system consists of a holographic phase mask fabricated by encoding the desired phase profiles into volume Bragg gratings, inserted in between two surface gratings. This device automatically adjusts each spectral component diffracted by the surface grating to the Bragg angle of the volume Bragg grating and equalizes phase incursion for all diffracted wavelengths. Transverse mode conversion is demonstrated and compared with theory for multiple narrow line laser sources operating from 488 to 1550 nm and for a broadband femtosecond source.

Wavefront shaping optical elements recorded in photo-thermo-refractive glass.

The paper presents an overview of the benefits of recording phase masks into the bulk of photo-thermo-refractive glass. We demonstrate that both binary and gray-scale phase masks can be encoded into the medium, and that such masks can be used for mode conversion and beam shaping with near-theoretical efficiency. We further demonstrate that by encoding the phase mask profile into a transmitting volume Bragg grating, it is possible to create tunable and achromatic phase masks without requiring a complex phase pattern.

Passively Q switched dual channel Tm:YLF laser by intracavity spectral beam combination with volume Bragg gratings.

A novel dual channel Tm:YLF laser system was developed where two degenerate laser cavities were coupled by spectrally beam combining their emission and by implementing a common output coupler. Under continuous wave running conditions, each channel's slope efficiency was greater than 45% and the maximum combined output power was 11 W. Passive Q-switching was achieved using an 80%, Cr:ZnSe saturable absorber. The output pulses had a maximum energy of 5.8 mJ and duration of 90 ns (~65 kW of peak power) at 5.7 W of absorbed pump power. Each channel showed less than 1 nm of spectral width with central wavelengths around 1880 nm and 1908 nm correspondingly. The system had adjustable spectral difference between the channels ranging from 5 to 20 nm which corresponds to 0.4 - 1.7 THz if the system is used for nonlinear difference frequency generation.

PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.

Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a human deafness gene, responsible for autosomal recessive deafness-124 (DFNB124). Sensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. PKHD1L1 is a stereocilia protein required for the formation of the developmentally transient stereocilia surface coat. In this study, we carry out an in depth characterization of PKHD1L1 expression in mice during development and adulthood, analyze hair-cell bundle morphology and hearing function in aging PKHD1L1-deficient mouse lines, and assess their susceptibility to noise damage. Our findings reveal that PKHD1L1-deficient mice display no disruption to bundle cohesion or tectorial membrane attachment-crown formation during development. However, starting from 6 weeks of age, PKHD1L1-deficient mice display missing stereocilia and disruptions to bundle coherence. Both conditional and constitutive PKHD1L1 knockout mice develop high-frequency hearing loss progressing to lower frequencies with age. Furthermore, PKHD1L1-deficient mice are susceptible to permanent hearing loss following moderate acoustic overexposure, which induces only temporary hearing threshold shifts in wild-type mice. These results suggest a role for PKHD1L1 in establishing robust sensory hair bundles during development, necessary for maintaining bundle cohesion and function in response to acoustic trauma and aging.

Elasticity and Thermal Stability are Key Determinants of Hearing Rescue by Mini-Protocadherin-15 Proteins.

Protocadherin-15 is a core protein component of inner-ear hair-cell tip links pulling on transduction channels essential for hearing and balance. Protocadherin-15 defects can result in non-syndromic deafness or Usher syndrome type 1F (USH1F) with hearing loss, balance deficits, and progressive blindness. Three rationally engineered shortened versions of protocadherin-15 (mini-PCDH15s) amenable for gene therapy have been used to rescue function in USH1F mouse models. Two can successfully or partially rescue hearing, while another one fails. Here we show that despite varying levels of hearing rescue, all three mini-PCDH15 versions can rescue hair-cell mechanotransduction. Negative-stain electron microscopy shows that all three versions form dimers like the wild-type protein, while crystal structures of some engineered fragments show that these can properly fold and bind calcium ions essential for function. In contrast, simulations predict distinct elasticities and nano differential scanning fluorimetry shows differences in melting temperature measurements. Our data suggest that elasticity and thermal stability are key determinants of sustained hearing rescue by mini-PCDH15s.

PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure.

Sensory hair cells of the cochlea are essential for hearing, relying on the mechanosensitive stereocilia bundle at their apical pole for their function. Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1) is a stereocilia protein required for normal hearing in mice, and for the formation of the transient stereocilia surface coat, expressed during early postnatal development. While the function of the stereocilia coat remains unclear, growing evidence supports PKHD1L1 as a human deafness gene. In this study we carry out in depth characterization of PKHD1L1 expression in mice during development and adulthood, analyze hair-cell bundle morphology and hearing function in aging PKHD1L1-defficient mouse lines, and assess their susceptibility to noise damage. Our findings reveal that PKHD1L1-deficient mice display no disruption to bundle cohesion or tectorial membrane attachment-crown formation during development. However, starting from 6 weeks of age, PKHD1L1-defficient mice display missing stereocilia and disruptions to bundle coherence. Both conditional and constitutive PKHD1L1 knock-out mice develop high-frequency hearing loss progressing to lower frequencies with age. Furthermore, PKHD1L1-deficient mice are susceptible to permanent hearing loss following moderate acoustic overexposure, which induces only temporary hearing threshold shifts in wild-type mice. These results suggest a role for PKHD1L1 in establishing robust sensory hair bundles during development, necessary for maintaining bundle cohesion and function in response to acoustic trauma and aging.

Post-stroke sleep disturbance and recurrent cardiovascular and cerebrovascular events: A systematic review and meta-analysis.

Despite improvements in survival rates, risk of recurrent events following stroke remains high. Identifying intervention targets to reduce secondary cardiovascular risk in stroke survivors is a priority. The relationship between sleep and stroke is complex: sleep disturbances are likely both a contributor to, and consequence of, stroke. The current aim was to examine the association between sleep disturbance and recurrent major acute coronary events or all-cause mortality in the post-stroke population. Thirty-two studies were identified, including 22 observational studies and 10 randomized clinical trials (RCTs). Identified studies included the following as predictors of post-stroke recurrent events: obstructive sleep apnea (OSA, n = 15 studies), treatment of OSA with positive airway pressure (PAP, n = 13 studies), sleep quality and/or insomnia (n = 3 studies), sleep duration (n = 1 study), polysomnographic sleep/sleep architecture metrics (n = 1 study), and restless legs syndrome (n = 1 study). A positive relationship of OSA and/or OSA severity with recurrent events/mortality was seen. Findings on PAP treatment for OSA were mixed. Positive findings indicating a benefit of PAP for post-stroke risk came largely from observational studies (pooled RR [95% CI] for association between PAP and recurrent cardiovascular event: 0.37 [0.17-0.79], I2 = 0%). Negative findings came largely from RCTs (RR [95% CI] for association between PAP and recurrent cardiovascular event + death: 0.70 [0.43-1.13], I2 = 30%). From the limited number of studies conducted to date, insomnia symptoms/poor sleep quality and long sleep duration were associated with increased risk. Sleep, a modifiable behavior, may be a secondary prevention target to reduce the risk of recurrent event and death following stroke. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021266558.

Diversity of developing peripheral glia revealed by single-cell RNA sequencing.

The peripheral nervous system responds to a wide variety of sensory stimuli, a process that requires great neuronal diversity. These diverse neurons are closely associated with glial cells originating from the neural crest. However, the molecular nature and diversity among peripheral glia are not understood. Here, we used single-cell RNA sequencing to profile developing and mature glia from somatosensory dorsal root ganglia and auditory spiral ganglia. We found that glial precursors (GPs) in these two systems differ in their transcriptional profiles. Despite their unique features, somatosensory and auditory GPs undergo convergent differentiation to generate molecularly uniform myelinating and non-myelinating Schwann cells. By contrast, somatosensory and auditory satellite glial cells retain system-specific features. Lastly, we identified a glial signature gene set, providing new insights into commonalities among glia across the nervous system. This survey of gene expression in peripheral glia constitutes a resource for understanding functions of glia across different sensory modalities.

Subtle Cerebellar Features in Relatives of Essential Tremor Cases.

Background: Essential tremor (ET) cases often exhibit a range of mild cerebellar signs. Their unaffected relatives have been shown in prior studies to exhibit subtle (i.e., preclinical) disease features. Objective: To quantify subtle cerebellar signs in unaffected first-degree relatives of ET cases stratified based on their tremor severity. Methods: Two hundred sixty-nine first-degree relatives of ET cases, none of whom reported tremor or a diagnosis of ET, or were diagnosed with ET based on detailed neurological examination, were stratified based on total tremor score (TTS) into two groups (lower TTS vs. higher TTS) and quartiles. Changes in gait, balance, and intention tremor were quantified on neurological examination. Results: Higher TTS performed worse on the tandem stance task (p = 0.011). When stratified into TTS quartiles, higher quartile was associated with worse performance in tandem stance (p = 0.011) and stance with feet together (p = 0.028). Similarly, intention tremor in the arms (p = 0.0002) and legs (p = 0.047) were higher in the groups with more tremor. Discussion: The links between ET and the cerebellum are multiple. These data provide intriguing evidence that subtle cerebellar signs (i.e., changes in balance and intention tremor) are more prevalent among first-degree relatives of ET cases with more tremor (i.e., those who may be themselves on the pathway to developing ET). These data contribute to a better characterization of what may be an early subclinical stage of the disease.

Severe Essential Tremor: Illustrative Videos.

Background: Essential tremor (ET) can be profoundly disabling in severe cases; however, such cases may not often be encountered by general practitioners, primary care physicians, or general neurologists, leading to misdiagnosis. Phenomenology shown: Severe kinetic, postural, and intention tremors in patients with ET. Educational value: To provide visual examples of severe, long-standing ET for general practitioners, primary care clinicians, and general neurologists.

Under-Recognition of Cervical Dystonia: An Essential Tremor Patient with Numerous Textbook Features of Cervical Dystonia.

Background: Physical examination findings of dystonia are often underrecognized, especially in the setting of other movement disorders such as essential tremor (ET). Phenomenology Shown: A patient with ET exhibited numerous textbook features of cervical dystonia, which were misattributed to ET by a primary care physician and two neurologists. Educational Value: To provide a clear and unmistakable visual example of the clinically significant characteristics of cervical dystonia in the setting of concomitant ET.