Black Sexual Minority Men's Experiences in MPowerment Interventions: Implications for HIV Prevention.

BACKGROUND: Black sexual minority men (BSMM) are disproportionately vulnerable to HIV acquisition; the MPowerment model is one community-based framework for preventing HIV in this population. It focuses on developing a supportive network of peers to promote health messaging, reduce stigma, and improve resilience. While these interventions have demonstrated general success, there are important challenges related to race, sexuality, and internalized stigma. Our study aimed to explore these experiences among BSMM in MPowerment models focused on HIV prevention. METHOD: We conducted 24 qualitative interviews of BSMM attending HIV prevention-related MPowerment events in the greater D.C. Metropolitan area. In-depth interviews were conducted via phone, and interviews were analyzed using thematic analysis. RESULTS: We identified four themes from the transcript analysis process: Black queer intersectional social support and community, HIV-related information and destigmatization, social status, and sexuality. Within each of these themes, we identified relationships with overall HIV prevention messaging, including barriers to PrEP use. Barriers related to social status were especially prevalent and described as unique to the D.C. metropolitan area. CONCLUSION: Overall, MPowerment event spaces provide a forum for BSMM to feel safe and supported while gaining important HIV-related knowledge and prevention access. Challenges related to social status and destigmatization of sexuality are important considerations in designing and implementing this model, especially related to PrEP promotion.

Stochastic and sinusoidal electrical stimuli increase the irregularity and gain of Type A and B medial vestibular nucleus neurons, in vitro.

Galvanic vestibular stimulation (GVS) has been shown to improve vestibular function potentially via stochastic resonance, however, it remains unknown how central vestibular nuclei process these signals. In vivo work applying electrical stimuli to the vestibular apparatus of animals has shown changes in neuronal discharge at the level of the primary vestibular afferents and hair cells. This study aimed to determine the cellular impacts of stochastic, sinusoidal, and stochastic + sinusoidal stimuli on individual medial vestibular nucleus (MVN) neurons of male and female C57BL/6 mice. All stimuli increased the irregularity of MVN neuronal discharge, while differentially affecting neuronal gain. This suggests that the heterogeneous MVN neuronal population (marked by differential expression of ion channels), may influence the impact of electrical stimuli on neuronal discharge. Neuronal subtypes showed increased variability of neuronal firing, where Type A and B neurons experienced the largest gain changes in response to stochastic and sinusoidal stimuli. Type C neurons were the least affected regarding neuronal firing variability and gain changes. The membrane potential (MP) of neurons was altered by sinusoidal and stochastic + sinusoidal stimuli, with Type B and C neuronal MP significantly affected. These results indicate that GVS-like electrical stimuli impact MVN neuronal discharge differentially, likely as a result of heterogeneous ion channel expression.

Splenius capitis: sensitive target for the cVEMP in older and neurodegenerative patients.

BACKGROUND: The vestibular evoked myogenic potential (VEMP) is a technique used to assess vestibular function. Cervical VEMPs (cVEMPs) are obtained conventionally from the sternocleidomastoid (SCM) muscle; however, the dorsal neck muscle splenius capitis (SPL) has also been shown to be a reliable target alongside the SCM in young subjects. OBJECTIVE: This study aimed to compare cVEMPs from the SCM and SPL in two positions across young, older, and Parkinson's disease (PD) patients. METHOD: Experiments were carried out using surface EMG electrodes placed over the SCM and SPL. cVEMPs were measured using a 30 s, 126 dB sound stimulus with 222 individual tone bursts, while subjects were in a supine and head-turned posture (also known as the head elevation method), and in a seated head-turned posture. RESULTS: When comparing cVEMPs across positions, the incidence of supine and seated SCM-cVEMPs diminished significantly in older and PD patients in comparison with young subjects. However, no statistically significant differences in incidences were found in seated SPL-cVEMPs when comparing young, older and PD patients. SPL-cVEMPs were present significantly more often than seated SCM-cVEMPs in PD patients. CONCLUSIONS: SPL-cVEMPs are not altered to the same extent that SCM-cVEMPs are by aging and disease and its addition to cVEMP testing may reduce false-positive tests for vestibulopathy.

Splenius capitis is a reliable target for measuring cervical vestibular evoked myogenic potentials in adults.

The cervical vestibular evoked myogenic potential (cVEMP) is a common and simple test of vestibulospinal reflex patency. In the clinic, cVEMPs are measured in response to loud sounds from the sternocleidomastoid (SCM) on the ventral neck, as subjects maintain an uncomfortable head posture needed to recruit SCM. Here we characterize the cVEMP in a dorsal neck turner (splenius capitis; SPL), and compare it with the SCM cVEMP. cVEMPs were recorded simultaneously via surface electromyography from SCM and SPL from 17 healthy subjects in a variety of postures, including head-turned postures adopted while either seated or standing, and the clinical posture. Like the SCM cVEMP recorded ipsilateral to the side of sound stimulation, the cVEMP on the contralateral SPL (synergistic with ipsilateral SCM) was characterized by a biphasic wave of muscle activity that began at ~ 13 ms. cVEMP reliability was higher on SPL vs. SCM in standing postures (chi-squared; P < 0.05), and equivalent results were obtained from SPL in a standing or seated posture. In 9 of the 17 subjects, we also obtained bilateral intramuscular (IM) recordings from SPL at the same time as the surface recordings. In these subjects, the initial surface response in SPL was associated with a consistent decrease in multi-unit IM SPL activity. Overall, these results demonstrate that SPL recordings offer a complimentary target for cVEMP assessments. The expression of SPL cVEMPs in simple head-turned postures may also improve the utility of cVEMP testing for vestibular assessment in children, the elderly, or non-compliant.

Monkeypox-Related Stigma and Vaccine Challenges as a Barrier to HIV Pre-Exposure Prophylaxis among Black Sexual Minority Men.

BACKGROUND: The U.S. monkeypox (mpox) outbreak of 2022 was a unique emergent public health crisis disproportionately affecting Black sexual minority men (BSMM). Similar to other stigmas, mpox-related stigma may have adverse effects on BSMM, including deterring HIV prevention such as PrEP. METHODS: Our study investigated the experiences and perceptions of BSMM related to mpox, including mpox-associated stigma, and PrEP engagement among BSMM. We conducted qualitative interviews of 24 BSMM attending HIV prevention-related events in the greater D.C. Metropolitan area. In-depth interviews were conducted via phone, and responses to questions specific to the mpox outbreak were analyzed using thematic analysis. RESULTS: We identified three key themes from the analysis: Mpox-related stigma, Mpox vaccine availability concerns, and Mpox vaccine hesitancy. Participants also described relationships between each of these three themes and PrEP use. Mpox stigma was particularly relevant as it is related to sexual stigma and is a deterrent to PrEP use. A sense of health system neglect of BSMM, especially related to low mpox vaccine availability, was also described. CONCLUSIONS: We identified mpox stigma and challenges related to mpox vaccination as key themes among BSMM, with implications for PrEP use. Future research exploring medical mistrust among BSMM, particularly related to HIV prevention, is recommended.

COVID-19, Vaccine Hesitancy, and HIV Pre-exposure Prophylaxis Among Black Sexual Minority Men.

BACKGROUND: The COVID-19 pandemic has created substantial and profound barriers to several forms of health care engagement. For Black sexual minority men, this may include engagement with pre-exposure prophylaxis (PrEP) to prevent HIV infection, with significant implications for HIV disparities. Our study explored how the COVID-19 pandemic affected Black sexual minority men, with a focus on relationships between COVID-19 and PrEP engagement. SETTING: We sampled 24 Black sexual minority men attending HIV prevention-related events in the greater D.C. Metropolitan area (D.C., Maryland, Virginia). METHODS: We conducted qualitative phone interviews among our sample. Questions were primarily focused on the COVID-19 pandemic and how it affected engagement and considerations of PrEP use. Interviews were transcribed and qualitatively analyzed using the 6 stages of thematic analysis. RESULTS: We identified 3 major themes from our thematic analysis: Changes in the health care system, changes in sexual and relationship contexts, and COVID-19 vaccine hesitancy and misinformation. Relationships between COVID-19 vaccine hesitancy and PrEP hesitancy were especially prevalent, with participants describing that COVID-19 hesitancy can directly deter PrEP use through eroding medical trust further. CONCLUSIONS: We identified changes in the health care system, sexual and relationship contexts, and COVID-19 vaccine hesitancy as important issues driven by COVID-19 with significant implications for PrEP use. The COVID-19 pandemic has changed the health care and social landscape in profound ways that affect PrEP access, sexual networks, and associated HIV vulnerability. Future research further exploring relationships between specific pandemic stressors and HIV prevention among Black sexual minority men is recommended .

Response characteristics of vestibular evoked myogenic potentials recorded over splenius capitis in young adults and adolescents.

BACKGROUND AND OBJECTIVES: Examine vestibular evoked myogenic potential (VEMP) responses recorded from surface electrodes over Splenius Capitis (SPC) in a seated position. SPECIFIC AIMS: (1) validate response characteristics of VEMP recordings from surface electrodes over Sternocleidomastoid (SCM) and over SCP and (2) assess age effects on responses in adolescents and young adults. MATERIALS AND METHODS: Simultaneous surface VEMP was recorded bilaterally from electrodes placed over the dorsal neck musculature at a location known from previous work to record from SPC in 15 healthy participants during trials with head rotation toward and away from the stimulated ear. VEMP was also recorded from electrodes over SCM, ipsilateral to the stimulus ear, in the same participants in a supine, head lift/turn position. RESULTS: Response amplitudes significantly increased with contraction strength and decreased with age. Participants were able to maintain sufficient contraction strength (amplitude) with head rotation to reliably measure over SPC. Normalized response amplitudes measured from electrodes over contralateral SPC were largest with head rotation contralateral to the stimulus ear. Normalized amplitudes and peak latencies were comparable to the same measures from SCM obtained in supine, head lift/turn position. CONCLUSIONS: Otolith generated myogenic responses can be recorded seated from electrodes over the dorsal neck with head rotation contralateral to the stimulus ear. In this position, contralateral recordings are consistent with responses known from previous work to arise from SPC; ipsilateral recordings may include crosstalk from activated muscles nearby, including ipsilateral SCM. Overall, techniques targeting contralateral SPC during contralateral head turn may provide additional methods of recording VEMPs.

Visual motion integration by neurons in the middle temporal area of a New World monkey, the marmoset.

The middle temporal area (MT/V5) is an anatomically distinct region of primate visual cortex that is specialized for the processing of image motion. It is generally thought that some neurons in area MT are capable of signalling the motion of complex patterns, but this has only been established in the macaque monkey. We made extracellular recordings from single units in area MT of anaesthetized marmosets, a New World monkey. We show through quantitative analyses that some neurons (35 of 185; 19%) are capable of signalling pattern motion ('pattern cells'). Across several dimensions, the visual response of pattern cells in marmosets is indistinguishable from that of pattern cells in macaques. Other neurons respond to the motion of oriented contours in a pattern ('component cells') or show intermediate properties. In addition, we encountered a subset of neurons (22 of 185; 12%) insensitive to sinusoidal gratings but very responsive to plaids and other two-dimensional patterns and otherwise indistinguishable from pattern cells. We compared the response of each cell class to drifting gratings and dot fields. In pattern cells, directional selectivity was similar for gratings and dot fields; in component cells, directional selectivity was weaker for dot fields than gratings. Pattern cells were more likely to have stronger suppressive surrounds, prefer lower spatial frequencies and prefer higher speeds than component cells. We conclude that pattern motion sensitivity is a feature of some neurons in area MT of both New and Old World monkeys, suggesting that this functional property is an important stage in motion analysis and is likely to be conserved in humans.

The impact of brief exposure to high contrast on the contrast response of neurons in primate lateral geniculate nucleus.

Prolonged exposure to an effective stimulus generally reduces the sensitivity of neurons early in the visual pathway. Yet eye and head movements bring about frequent changes in the retinal image, and it is less clear that exposure to brief presentations will produce similar desensitization. To address this, we made extracellular recordings from single neurons in the lateral geniculate nucleus of anesthetized marmosets, a New World primate. We measured the contrast response for drifting gratings before and after 0.5-s exposure to a high-contrast drifting grating, a stationary grating, or a blank screen. Prior exposure to the drifting grating reduced the contrast sensitivity of cells in the magnocellular pathway, on average by 23%; this reduction remained strong when the adapting and test stimuli were separated by 0.4 s. Exposure to a stationary grating of the preferred spatial phase did not change the contrast response; exposure to the opposite spatial phase did. None of the brief adaptors reduced the sensitivity of parvocellular cells. We conclude that brief periods of high contrast, such as those that would be expected to occur during a normal visual fixation, are sufficient to reduce the sensitivity of magnocellular-pathway cells.

Summating potentials from the utricular macula of anaesthetized guinea pigs.

The Summating Potential (SP) was first recorded in the cochlea in the 1950s and represents an objective measure of cochlear hair cell function, in vivo. Despite being a regular tool in hearing research, a similar response has not yet been recorded from the vestibular system. This is mainly due to the lack of experimental techniques available to record electrical vestibular hair cell responses in isolation from the much larger cochlear potentials. Here we demonstrate the first recordings of the vestibular SP, evoked by Bone-Conducted Vibration (BCV) and Air-Conducted Sound (ACS) stimuli, in anaesthetized guinea pigs. Field potential measurements were taken from the basal surface of the utricular macula, and from the facial nerve canal following surgical or chemical ablation of the cochlea. SPs were evoked by stimuli with frequencies above ~200 Hz, and only with moderate to high intensity (~0.005-0.05 g) BCV and ACS (~120-140 dB SPL). Neural blockade abolished the Vestibular short-latency Evoked Potential (VsEP) and Vestibular Nerve Neurophonic (VNN) from the facial nerve canal recordings but did not abolish the vestibular SP nor the vestibular microphonic. Importantly, the vestibular SP was irreversibly abolished from the utricle and facial nerve canal recordings following local gentamicin application, highlighting its hair cell origin. This is the first study to record the Summating Potential from the mammalian vestibular system, in vivo, providing a novel research tool to assess vestibular hair cell function during experimental manipulations and animal models of disease.

Response characteristics of vestibular evoked myogenic potentials recorded over splenius capitis in young adults and adolescents.

BACKGROUND AND OBJECTIVES: Examine vestibular evoked myogenic potential (VEMP) responses recorded from surface electrodes over Splenius Capitis (SPC) in a seated position. SPECIFIC AIMS: (1) validate response characteristics of VEMP recordings from surface electrodes over Sternocleidomastoid (SCM) and over SCP and (2) assess age effects on responses in adolescents and young adults. MATERIALS AND METHODS: Simultaneous surface VEMP was recorded bilaterally from electrodes placed over the dorsal neck musculature at a location known from previous work to record from SPC in 15 healthy participants during trials with head rotation toward and away from the stimulated ear. VEMP was also recorded from electrodes over SCM, ipsilateral to the stimulus ear, in the same participants in a supine, head lift/turn position. RESULTS: Response amplitudes significantly increased with contraction strength and decreased with age. Participants were able to maintain sufficient contraction strength (amplitude) with head rotation to reliably measure over SPC. Normalized response amplitudes measured from electrodes over contralateral SPC were largest with head rotation contralateral to the stimulus ear. Normalized amplitudes and peak latencies were comparable to the same measures from SCM obtained in supine, head lift/turn position. CONCLUSIONS: Otolith generated myogenic responses can be recorded seated from electrodes over the dorsal neck with head rotation contralateral to the stimulus ear. In this position, contralateral recordings are consistent with responses known from previous work to arise from SPC; ipsilateral recordings may include crosstalk from activated muscles nearby, including ipsilateral SCM. Overall, techniques targeting contralateral SPC during contralateral head turn may provide additional methods of recording VEMPs.

Adaptable mechanisms that regulate the contrast response of neurons in the primate lateral geniculate nucleus.

The response of the classical receptive field of visual neurons can be suppressed by stimuli that, when presented alone, cause no change in the discharge rate. This suppression reveals the presence of an extraclassical receptive field (ECRF). In recordings from the lateral geniculate nucleus (LGN) of a New World primate, the marmoset, we characterize the mechanisms that contribute to the ECRF by measuring their spatiotemporal tuning during prolonged exposure to a high-contrast grating (contrast adaptation). The ECRF was strongest in magnocellular cells, where contrast adaptation reduced suppression from the ECRF: adaptation of the ECRF transferred across spatial frequency, temporal frequency, and orientation, but not across space. This implies that the ECRF of LGN cells comprises multiple adaptable mechanisms, each broadly tuned but spatially localized, and consistent with a retinal origin. Signals from the ECRF saturated at high contrasts, and so adaptation of one part of the ECRF brought into its operating range signals from other parts of the visual field. Although the ECRF is adaptable, its major impact during contrast adaptation to a spatially extended pattern was to reduce visual response and hence reduce a neuron's susceptibility to contrast adaptation; in normal viewing, a major role of the ECRF might be to protect visual sensitivity in scenes dominated by high contrast.

Linear and nonlinear contributions to the visual sensitivity of neurons in primate lateral geniculate nucleus.

Several parallel pathways convey retinal signals to the visual cortex of primates. The signals of the parvocellular (P) and magnocellular (M) pathways are well characterized; the properties of other rarely encountered cell types are distinctive in many ways, but it is not clear that they can provide signals with the same fidelity. Here we study this by characterizing the temporal receptive field of neurons in the lateral geniculate nucleus of anesthetized marmosets. For each neuron, we measured the response to a flickering uniform field, and, from this, estimated the linear and nonlinear receptive fields using spike-triggered average (STA) and spike-triggered covariance (STC) analyses. As expected the response of most P-cells was dominated by the STA, but the response of most M-cells required additional nonlinear components, and these usually acted to suppress cell responses. The STC analysis showed stronger suppressive axes in suppressed-by-contrast cells, and both suppressive and excitatory axes in on-off cells. Together, the STA and the STC analyses form a model of the temporal response to a large uniform field: under this model, the information that was provided by suppressed-by-contrast cells or on-off cells approached that provided by the P- and M-cells. However, whereas P- and M-cells provided more information about luminance, the nonlinear cells provided more information about the contrast energy. This suggests that the nonlinear cells provide complimentary signals to those of P- and M-cells, with reasonably high fidelity, and may play an important role in normal visual processing.

Vitamin D-fence.

The role of vitamin D in the immune system is complex. Vitamin D is produced in the skin following exposure to ultraviolet radiation. There is compelling evidence that vitamin D compounds protect against ultraviolet radiation-induced DNA damage and immune suppression, suggesting it may be beneficial as a skin cancer preventive agent. However, vitamin D has many modulatory effects on the immune system and it has in fact been suggested that the immune suppression generally attributed to the UVB portion of sunlight is mediated through vitamin D. Here we describe the role of vitamin D compounds as "defence" molecules against UVR-induced damage, and investigate both sides of the "fence" regarding the effects of vitamin D compounds and the immune system.

The intrinsic plasticity of medial vestibular nucleus neurons during vestibular compensation-a systematic review and meta-analysis.

BACKGROUND: Vestibular compensation is a homeostatic process that occurs in the central nervous system in response to peripheral vestibular dysfunction. Experimental studies in rodent models have suggested that unilateral peripheral vestibular lesions are correlated with an increase in the intrinsic excitability of central vestibular neurons. This process may be dependent on the intrinsic properties of the neurons themselves. We aimed to conduct a systematic review of the literature to survey the evidence for changes in intrinsic plasticity observed during the acute phase of vestibular compensation. METHODS: We systematically reviewed the literature regarding the electrophysiological effect of experimentally induced unilateral vestibular deafferentation (UVD) on the intrinsic membrane properties of medial vestibular nucleus neurons in animal models. We developed tools to assess the methodological quality (precision, validity and bias) of studies that met pre-determined inclusion and exclusion criteria. We extracted numerical data and performed a meta-analysis of specific quantitative data pooled from these studies. RESULTS: We identified 17 studies that satisfied the inclusion criteria. There is moderate quality evidence to suggest a statistically significant increase in the intrinsic excitability of medial vestibular nucleus neurons following unilateral vestibular deafferentation. Specifically, the spontaneous discharge rate increases by 4 spikes/s on average and the sensitivity to current stimuli increases. CONCLUSION: Using this novel approach, we demonstrate that the methodology of systematic review and meta-analysis is a useful tool in the summation of data across experimental animal studies with similar aims.

Elucidating the time course of the transcriptomic response to photobiomodulation through gene co-expression analysis.

Photobiomodulation (PBM) with low-intensity red to near infrared light elicits neuroprotection in various pre-clinical models and in some clinical contexts, yet the intracellular mechanisms triggered by PBM, and their temporal sequence of modulation, remain unclear. We aimed to address this uncertainty by mapping the temporal transcriptomic response to PBM. Human SH-SY5Y neuroblastoma cells were treated with 670 nm PBM and RNA collected a various time points over 24 h. The transcriptome was screened by RNA microarray, and gene co-expression analysis by hierarchical clustering was coupled with bioinformatics analysis to reveal the molecular systems modulated by PBM and their expression patterns over the time course. The findings suggest that PBM induces distinct early phase (up to 8 h post-PBM) and late phase (24 h post-PBM) intracellular responses. The early intracellular response features enrichment of pathways relating to transcriptional regulation and cellular stress responses, while the late intracellular response demonstrates a physiological shift to enrichment of downstream pathways such as cell death and DNA damage. These findings provide support for the hypothesis that PBM acts as a transient stressful stimulus, activating endogenous stress response pathways that in turn enhance cellular resilience. Further, the study introduces a novel method for retaining the richness of the temporal component when analysing transcriptomic time course data sets.

Utricular Sensitivity during Hydrodynamic Displacements of the Macula.

To explore the effects of cochlear hair cell displacement, researchers have previously monitored functional and mechanical responses during low-frequency (LF) acoustic stimulation of the cochlea. The induced changes are believed to result from modulation of the conductance of mechano-electrical transduction (MET) channels on cochlear hair cells, along with receptor potential modulation. It is less clear how, or if, vestibular hair cell displacement affects vestibular function. Here, we have used LF (<20 Hz) hydrodynamic modulation of the utricular macula position, whilst recording functional and mechanical responses, to investigate the effects of utricular macula displacement. Measured responses included the Utricular Microphonic (UM), the vestibular short-latency evoked potential (VsEP), and laser Doppler vibrometry recordings of macular position. Over 1 cycle of the LF bias, the UM amplitude and waveform were cyclically modulated, with Boltzmann analysis suggesting a cyclic modulation of the vestibular MET gating. The VsEP amplitude was cyclically modulated throughout the LF bias, demonstrating a relative increase (~20-50 %; re baseline) and decrease (~10-20 %; re baseline), which is believed to be related to the MET conductance and vestibular hair cell sensitivity. The relationship between macular displacement and changes in UM and VsEP responses was consistent within and across animals. These results suggest that the sensory structures underlying the VsEP, often thought to be a cranial jerk-sensitive response, are at least partially sensitive to LF (and possibly static) pressures or motion. Furthermore, these results highlight the possibility that some of the vestibular dysfunction related to endolymphatic hydrops may be due to altered vestibular transduction following mechanical (or morphological) changes in the labyrinth.

K369I Tau Mice Demonstrate a Shift Towards Striatal Neuron Burst Firing and Goal-directed Behaviour.

Pathological forms of the microtubule-associated protein tau are involved in a large group of neurodegenerative diseases named tauopathies, including frontotemporal lobar degeneration (FTLD-tau). K369I mutant tau transgenic mice (K3 mice) recapitulate neural and behavioural symptoms of FTLD, including tau aggregates in the cortex, alterations to nigrostriatum, memory deficits and parkinsonism. The aim of this study was to further characterise the K3 mouse model by examining functional alterations to the striatum. Whole-cell patch-clamp electrophysiology was used to investigate the properties of striatal neurons in K3 mice and wildtype controls. Additionally, striatal-based instrumental learning tasks were conducted to assess goal-directed versus habitual behaviours (i.e., by examining sensitivity to outcome devaluation and progressive ratios). The K3 model demonstrated significant alterations in the discharge properties of striatal neurons relative to wildtype mice, which manifested as a shift in neuronal output towards a burst firing state. K3 mice acquired goal-directed responding faster than control mice and were goal-directed at test unlike wildtype mice, which is likely to indicate reduced capacity to develop habitual behaviour. The observed pattern of behaviour in K3 mice is suggestive of deficits in dorsal lateral striatal function and this was supported by our electrophysiological findings. Thus, both the electrophysiological and behavioural alterations indicate that K3 mice have early deficits in striatal function. This finding adds to the growing literature which indicate that the striatum is impacted in tau-related neuropathies such as FTLD, and further suggests that the K3 model is a unique mouse model for investigating FTLD especially with striatal involvement.