Vesicular glutamatergic transmission in noise-induced loss and repair of cochlear ribbon synapses

Noise-induced excitotoxicity is thought to depend on glutamate. However, the excitotoxic mechanisms are unknown, and the necessity of glutamate for synapse loss or regeneration is unclear. Despite absence of glutamatergic transmission from cochlear inner hair cells in mice lacking the vesicular glutamate transporter-3

Representation and Outcome of Catheter Ablation for Treatment of Atrial Fibrillation Among Patients with Obesity: A Systematic Review of Randomized Control Studies

https://digitalcommons.unmc.edu/surp2022/1018/thumbnail.jp

Maturation of heterogeneity in afferent synapse ultrastructure in the mouse cochlea

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured the size, shape, vesicle content, and position of 70 ribbon synapses from the mid-cochlea. Several features matured over late postnatal development. From p17 to p34, presynaptic densities (PDs) and post-synaptic densities (PSDs) became smaller on average (PDs: 0.75 to 0.33; PSDs: 0.58 to 0.31 μ

Individual and partner risk factors associated with abnormal cervical cytology among women in HIV-discordant relationships

Individual and sexual partner characteristics may increase risk of abnormal cervical cytology among women in HIV-discordant relationships. Papanicolaou smears were obtained in a prospective cohort of Kenyan HIV-discordant couples. Of 441 women, 283 (64%) were HIV-infected and 158 (36%) were HIV-uninfected with HIV-infected partners. Overall, 79 (18%) had low-grade and 25 (6%) high-grade cervical abnormalities. Lack of male circumcision, male HSV-2 seropositivity and lower couple socioeconomic status were associated with cervical abnormalities (p350 cells/µL) had the lowest prevalence of high-grade cervical lesions. HIV-infected women (CD4>350 cells/µL) and HIV-uninfected women with HIV-infected partners (CD4≤350 cells/µL) were at similar intermediate risk (P>0.05), and HIV-infected women (CD4≤350 cells/µL) had significantly higher risk of high-grade cervical abnormalities (p=0.05). Women in HIV-discordant relationships have high rates of cervical lesions and this may be influenced by couple-level factors, including HIV status and CD4 count of the infected partner

Combined optogenetic and electrical stimulation of the sciatic nerve for selective control of sensory fibers

IntroductionElectrical stimulation offers a drug-free alternative for the treatment of many neurological conditions, such as chronic pain. However, it is not easy to selectively activate afferent or efferent fibers of mixed nerves, nor their functional subtypes. Optogenetics overcomes these issues by controlling activity selectively in genetically modified fibers, however the reliability of responses to light are poor compared to electrical stimulation and the high intensities of light required present considerable translational challenges. In this study we employed a combined protocol of optical and electrical stimulation to the sciatic nerve in an optogenetic mouse model to allow for better selectivity, efficiency, and safety to overcome fundamental limitations of electrical-only and optical-only stimulation.MethodsThe sciatic nerve was surgically exposed in anesthetized mice (n = 12) expressing the ChR2-H134R opsin via the parvalbumin promoter. A custom-made peripheral nerve cuff electrode and a 452 nm laser-coupled optical fiber were used to elicit neural activity utilizing optical-only, electrical-only, or combined stimulation. Activation thresholds for the individual and combined responses were measured.ResultsOptically evoked responses had a conduction velocity of 34.3 m/s, consistent with ChR2-H134R expression in proprioceptive and low-threshold mechanoreceptor (Aα/Aβ) fibers which was also confirmed via immunohistochemical methods. Combined stimulation, utilizing a 1 ms near-threshold light pulse followed by an electrical pulse 0.5 ms later, approximately halved the electrical threshold for activation (p = 0.006, n = 5) and resulted in a 5.5 dB increase in the Aα/Aβ hybrid response amplitude compared to the electrical-only response at equivalent electrical levels (p = 0.003, n = 6). As a result, there was a 3.25 dB increase in the therapeutic stimulation window between the Aα/Aβ fiber and myogenic thresholds (p = 0.008, n = 4).DiscussionThe results demonstrate that light can be used to prime the optogenetically modified neural population to reside near threshold, thereby selectively reducing the electrical threshold for neural activation in these fibers. This reduces the amount of light needed for activation for increased safety and reduces potential off-target effects by only stimulating the fibers of interest. Since Aα/Aβ fibers are potential targets for neuromodulation in chronic pain conditions, these findings could be used to develop effective strategies to selectively manipulate pain transmission pathways in the periphery

Anal Examinations in Cases of Alleged Homosexuality

Anal examinations are forcibly conducted in many countries where consensual anal intercourse is considered a criminal act. They are conducted almost exclusively on males in an effort to “prove” that they are “homosexuals” despite the fact that anal intercourse is not a necessary determinant of “homosexual activity.” Forcibly conducted anal examinations are usually initiated at the request of law enforcement officials, the prosecutor, or the court and conducted in the absence of informed consent or in circumstances where individuals are not capable of giving genuine informed consent or where refusal to give consent would be interpreted as self-incrimination. This may be presumed to be the case when examinations are conducted on individuals in detention, subsequent to allegations of criminalised sexual acts by the authorities. The purpose of this medico-legal statement is to provide legal experts, adjudicators, health care professionals, and policymakers, among others, with an understanding of: 1) the validity of forcibly conducted anal examinations as medical and scientific evidence of consensual anal intercourse; 2) the likely physical and psychological consequences of forcibly conducted anal examinations; and 3) whether, based on these effects, forcibly conducted anal examination constitutes cruel, inhuman, or degrading treatment or torture

Next Generation Flight Controller Trainer System

The Next Generation Flight Controller Trainer (NGFCT) is a relatively inexpensive system of hardware and software that provides high-fidelity training for spaceshuttle flight controllers. NGFCT provides simulations into which are integrated the behaviors of emulated space-shuttle vehicle onboard general-purpose computers (GPCs), mission-control center (MCC) displays, and space-shuttle systems as represented by high-fidelity shuttle mission simulator (SMS) mathematical models. The emulated GPC computers enable the execution of onboard binary flight-specific software. The SMS models include representations of system malfunctions that can be easily invoked. The NGFCT software has a flexible design that enables independent updating of its GPC, SMS, and MCC components

Statement on Virginity Testing: Independent Forensic Expert Group

Virginity examinations are practiced in many countries, and often forcibly, in a number of contexts, including in detention places; on women who allege rape; on women who are accused by authorities of prostitution; and as part of public or social policies to control sexuality. In other states, the practice is illegal. The purpose of this medico-legal statement is to provide legal experts, adjudicators, healthcare professionals, and policymakers, among others, with an understanding of the physical and psychological effects of forcibly conducting virginity examinations on females and to assess whether, based on these effects, forcibly conducted virginity examinations constitute cruel, inhuman, or degrading treatment or torture. This medico-legal statement also addresses the medical interpretation and relevance of such examinations and the ethical implications. This opinion considers an examination to be ‘forcibly conducted’ when it is “committed by force, or by threat of force or coercion, such as caused by fear of violence, duress, detention, psychological oppression or abuse of power, against such person incapable of giving genuine consent.”   For full details about the Independent Forensic Expert Group please visit http://www.irct.org/our-support/ medical-and-psychological-case-support/forensic-expertgroup.aspx

ASASSN-14ko is a Periodic Nuclear Transient in ESO 253-G003

We present the discovery that ASASSN-14ko is a periodically flaring AGN at the center of the galaxy ESO 253-G003. At the time of its discovery by the All-Sky Automated Survey for Supernovae (ASAS-SN), it was classified as a supernova close to the nucleus. The subsequent six years of V- and g-band ASAS-SN observations reveal that ASASSN-14ko has nuclear flares occurring at regular intervals. The seventeen observed outbursts show evidence of a decreasing period over time, with a mean period of $P_0 = 114.2 \pm 0.4$ days and a period derivative of $\dot{P} = -0.0017\pm0.0003$. The most recent outburst in May 2020, which took place as predicted, exhibited spectroscopic changes during the rise and a had a UV bright, blackbody spectral energy distribution similar to tidal disruption events (TDEs). The X-ray flux decreased by a factor of 4 at the beginning of the outburst and then returned to its quiescent flux after ~8 days. TESS observed an outburst during Sectors 4-6, revealing a rise time of $5.60 \pm 0.05$ days in the optical and a decline that is best fit with an exponential model. We discuss several possible scenarios to explain ASASSN-14ko's periodic outbursts, but currently favor a repeated partial TDE. The next outbursts should peak in the optical on UT 2020-09-7.4$\pm$1.1 and UT 2020-12-26.5$\pm$1.4.Comment: 26 pages, 15 figures, 7 tables. Will be submitted to ApJ. The latest flare is currently ongoing, as we predicte