Distinct Manifestations of Cooperative, Multidimensional Stimulus Representations in Different Auditory Forebrain Stations.

Classic spectrotemporal receptive fields (STRFs) for auditory neurons are usually expressed as a single linear filter representing a single encoded stimulus feature. Multifilter STRF models represent the stimulus-response relationship of primary auditory cortex (A1) neurons more accurately because they can capture multiple stimulus features. To determine whether multifilter processing is unique to A1, we compared the utility of single-filter versus multifilter STRF models in the medial geniculate body (MGB), anterior auditory field (AAF), and A1 of ketamine-anesthetized cats. We estimated STRFs using both spike-triggered average (STA) and maximally informative dimension (MID) methods. Comparison of basic filter properties of first maximally informative dimension (MID1) and second maximally informative dimension (MID2) in the 3 stations revealed broader spectral integration of MID2s in MGBv and A1 as opposed to AAF. MID2 peak latency was substantially longer than for STAs and MID1s in all 3 stations. The 2-filter MID model captured more information and yielded better predictions in many neurons from all 3 areas but disproportionately more so in AAF and A1 compared with MGBv. Significantly, information-enhancing cooperation between the 2 MIDs was largely restricted to A1 neurons. This demonstrates significant differences in how these 3 forebrain stations process auditory information, as expressed in effective and synergistic multifilter processing.

Primary auditory cortical responses to electrical stimulation of the thalamus.

Cochlear implant electrical stimulation of the auditory system to rehabilitate deafness has been remarkably successful. Its deployment requires both an intact auditory nerve and a suitably patent cochlear lumen. When disease renders prerequisite conditions impassable, such as in neurofibromatosis type II and cochlear obliterans, alternative treatment targets are considered. Electrical stimulation of the cochlear nucleus and midbrain in humans has delivered encouraging clinical outcomes, buttressing the promise of central auditory prostheses to mitigate deafness in those who are not candidates for cochlear implantation. In this study we explored another possible implant target: the auditory thalamus. In anesthetized cats, we first presented pure tones to determine frequency preferences of thalamic and cortical sites. We then electrically stimulated tonotopically organized thalamic sites while recording from primary auditory cortical sites using a multichannel recording probe. Cathode-leading biphasic thalamic stimulation thresholds that evoked cortical responses were much lower than published accounts of cochlear and midbrain stimulation. Cortical activation dynamic ranges were similar to those reported for cochlear stimulation, but they were narrower than those found through midbrain stimulation. Our results imply that thalamic stimulation can activate auditory cortex at low electrical current levels and suggest an auditory thalamic implant may be a viable central auditory prosthesis.

Racial Disparities in 30-day Readmissions after Surgery for Head and Neck Cancer.

BACKGROUND: Native Hawaiians and other Pacific Islanders (NHPI) patients with head and neck cancer are often aggregated with Asian individuals despite evidence of heterogeneous health outcomes and mortality. The aim of this study was to determine the association of race with unplanned 30-day hospital readmission rate after head and neck surgery across the five federally recognized racial categories. METHODS: This retrospective cohort study used a national hospital-based database and included patients ≥18 years old with diagnostically confirmed, nonmetastatic head and neck cancer of any subsite treated surgically between 2004 and 2017. The primary endpoint was unplanned readmission within 30 days of discharge after primary surgery. RESULTS: A total of 365,834 patients were included who were predominantly White (87%), treated at academic cancer centers (47%), lower income (63%), with early-stage disease (60%), and with thyroid (47%) or oral cavity (23%) cancers. Median follow-up duration was 47 months. Of the 10,717 (3%) readmissions, 5,845 (1.6%) were unplanned. Adjusted for confounders and compared with White patients, NHPI patients had the highest likelihood of unplanned (aOR 2.07, 95%CI 1.16-3.40, p = 0.008) readmissions. Within the NHPI group, patients with lower income (aOR 4.27, 95%CI 1.28-20.4, p = 0.035) and those residing in an urban or rural area (aOR 7.42, 95%CI 1.14-49.5, p = 0.034) were more likely to be readmitted. CONCLUSIONS: NHPI patients with head and neck cancers experience significantly higher 30-day readmissions following definitive surgical treatment. These results highlight the importance of racial disaggregation in clinical studies. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1282-1287, 2024.

"Hate has chipped away at my sense of security": A survey study of the impacts of anti-Asian hate on the health of older Asians.

BACKGROUND: Since the beginning of the COVID-19 pandemic, older Asians have experienced a rise in racism and discrimination based on their race and ethnicity. This study examines how anti-Asian hate impacts older Asians' mental, social, and physical health. METHODS: From March 18, 2022 to January 24, 2023, we conducted a cross-sectional survey study of community-dwelling Asian/Asian American adults aged ≥50 years from the San Francisco Bay Area. Measures included perceptions of anti-Asian hate; direct encounters with hate incidents; indirect experiences with hate incidents (e.g. knowing a friend who was a victim); reports of anxiety, depression, loneliness, and changes in daily activities; ways to address these issues; and discussions with clinicians about hate incidents. RESULTS: Of the 293 older Asians, 158 (54%) were Vietnamese and 97 (33%) Chinese. Eighty-five (29%) participants were direct victims of anti-Asian hate, 112 (38%) reported anxiety, 105 (36%) reported depression, 161 (55%) reported loneliness, and 142 (48%) reported decreased daily activities. Compared with those who were "not-at-all" to "moderately" worried about hate incidents, participants who were "very" to "extremely" worried experienced heightened anxiety (42% versus 16%), loneliness (30% versus 14%), and changes in daily activities (66% versus 31%), p < 0.01 for all. Most participants (72%) felt comfortable discussing hate incidents with clinicians; however, only 31 (11%) reported that a clinician had talked with them about these incidents. CONCLUSION: Both directly and indirectly, anti-Asian hate negatively impacts older Asians' mental, social, and physical health. Clinicians have a role in addressing the health impacts of anti-Asian hate.

Race and Ethnicity Representation in Phase 2/3 Oncology Clinical Trial Publications: A Systematic Review.

Importance: The five 1997 Office of Management and Budget races in the US include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White, with Hispanic ethnicity. Despite the Affordable Care Act mandating Office of Management and Budget-based collecting and reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity. Objective: To quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials. Evidence Review: In this systematic review, PubMed and Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid cancers, published between January 1, 2012, and December 31, 2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in each clinical trial publication by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov. Findings: Among 1202 publications evaluated, 364 met inclusion criteria: 16 JAMA, 241 Journal of Clinical Oncology, 19 Lancet, and 88 New England Journal of Medicine. Publications included 268 209 patients (171 132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included American Indian or Alaska Native in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), Native Hawaiian or Other Pacific Islander in 28 (8%), and White in 254 (70%). Median RQ varied across race (P < .001 BC), with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients. Sensitivity analyses showed similar findings on subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for American Indian or Alaska Native (14% vs 45%; P < .001 per McNemar χ2 test with continuity correction [MC]) and Native Hawaiian or Other Pacific Islander (8% vs 43%; P < .001 MC). Conclusions and Relevance: While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with Affordable Care Act-concordant race and ethnicity federal reporting requirements.

Comparison of the respiratory bacterial microbiome in cats with feline asthma and chronic bronchitis.

Objectives: While feline chronic bronchitis (CB) is known as neutrophilic bronchial inflammation (NI), feline asthma (FA) is defined as an eosinophilic airway inflammation (EI). Feline chronic bronchial disease refers to both syndromes, with similar clinical presentations and applied treatment strategies. Recent studies described alterations of the microbiota composition in cats with FA, but little is known about the comparison of the lung microbiota between different types of feline bronchial disease. The study aimed to describe the bacterial microbiota of the lower respiratory tracts of cats with FA and CB and to identify potential differences. Methods: Twenty-two client-owned cats with FA (n = 15) or CB (n = 7) confirmed via bronchoalveolar-lavage (BALF)-cytology were included. Next-generation sequencing analysis of 16S rRNA genes was performed on bacterial DNA derived from BALF samples. QIIME was used to compare microbial composition and diversity between groups. Results: Evenness and alpha-diversity-indices did not significantly differ between cats with FA and CB (Shannon p = 0.084, Chao 1 p = 0.698, observed ASVs p = 0.944). Based on a PERMANOVA analysis, no significant differences were observed in microbial composition between animals of both groups (Bray-Curtis metric, R-value 0.086, p = 0.785; unweighted UniFrac metric, R-value -0.089, p = 0.799; weighted Unifrac metric, R-value -0.072, p = 0.823). Regarding taxonomic composition, significant differences were detected for Actinobacteria on the phylum level (p = 0.026), Mycoplasma spp. (p = 0.048), and Acinetobacteria (p = 0.049) on the genus level between cats with FA and CB, with generally strong interindividual differences seen. There was a significant difference in the duration of clinical signs before diagnosis in animals dominated by Bacteriodetes (median 12 months, range 2-58 months) compared to animals dominated by Proteobacteria (median 1 month, range 1 day to 18 months; p = 0.003). Conclusions and relevance: Lung microbiota composition is very similar in cat populations with spontaneous FA and CB besides small differences in some bacterial groups. However, with disease progression, the lung microbiome of cats with both diseases appears to shift away from dominantly Proteobacteria to a pattern more dominated by Bacteriodetes. A substantial proportion of cats tested positive for Mycoplasma spp. via sequencing, while none of them tested positive using classical PCR.

Creation of an ustekinumab external control arm for Crohn's disease using electronic health records data: A pilot study.

BACKGROUND: Randomized trials are the gold-standard for clinical evidence generation, but they can sometimes be limited by infeasibility and unclear generalizability to real-world practice. External control arm (ECA) studies may help address this evidence gaps by constructing retrospective cohorts that closely emulate prospective ones. Experience in constructing these outside the context of rare diseases or cancer is limited. We piloted an approach for developing an ECA in Crohn's disease using electronic health records (EHR) data. METHODS: We queried EHR databases and manually screened records at the University of California, San Francisco to identify patients meeting the eligibility criteria of TRIDENT, a recently completed interventional trial involving an ustekinumab reference arm. We defined timepoints to balance missing data and bias. We compared imputation models by their impacts on cohort membership and outcomes. We assessed the accuracy of algorithmic data curation against manual review. Lastly, we assessed disease activity following treatment with ustekinumab. RESULTS: Screening identified 183 patients. 30% of the cohort had missing baseline data. Nonetheless, cohort membership and outcomes were robust to the method of imputation. Algorithms for ascertaining non-symptom-based elements of disease activity using structured data were accurate against manual review. The cohort consisted of 56 patients, exceeding planned enrollment in TRIDENT. 34% of the cohort was in steroid-free remission at week 24. CONCLUSION: We piloted an approach for creating an ECA in Crohn's disease from EHR data by using a combination of informatics and manual methods. However, our study reveals significant missing data when standard-of-care clinical data are repurposed. More work will be needed to improve the alignment of trial design with typical patterns of clinical practice, and thereby enable a future of more robust ECAs in chronic diseases like Crohn's disease.

Functional networks of parvalbumin-immunoreactive neurons in cat auditory cortex.

Inhibitory interneurons constitute ∼20% of auditory cortical cells and are essential for shaping sensory processing. Connectivity patterns of interneurons in relation to functional organization principles are not well understood. We contrasted the connection patterns of parvalbumin-immunoreactive cells in two functionally distinct cortical regions: the tonotopic, narrowly frequency-tuned module [central narrow band (cNB)] of cat central primary auditory cortex (AI) and the nontonotopic, broadly tuned second auditory field (AII). Interneuronal connectivity patterns and laminar distribution were identified by combining a retrograde tracer (wheat-germ agglutinin apo-horseradish peroxidase colloidal gold) with labeling of the Ca(2+) binding protein parvalbumin (Pv), a marker for the GABAergic interneurons usually described physiologically as fast-spiking neurons. In AI, parvalbumin-positive (Pv+) cells constituted 13% of the retrograde labeled cells in the immediate vicinity of the injection site, compared to 10% in AII. The retrograde labeling of Pv+ cells along isofrequency countours was confined to the cNB. The spatial spread of labeled excitatory neurons in AI was more than twice that found for Pv+ cells. By contrast, in the AII, the spread of Pv+ cells was nearly equal to that of excitatory neurons. The retrograde labeling of Pv+ cells was anisotropic in AI and isotropic in AII. This demonstration of inhibitory networks in auditory cortex reveals that the connections of cat GABAergic AI and AII cells follow different anatomical plans and thus contribute differently to the shaping of neural response properties. The finding that local connectivity of parvalbumin-immunoreactive neurons in AI is closely aligned with spectral integration properties demonstrates the critical role of inhibition in creating distinct processing modules in AI.

Improved stimulus representation by short interspike intervals in primary auditory cortex.

We analyzed the receptive field information conveyed by interspike intervals (ISIs) in the auditory cortex. In the visual system, different ISIs may both code for different visual features and convey differing amounts of stimulus information. To determine their potential role in auditory signal processing, we obtained extracellular recordings in the primary auditory cortex (AI) of the cat while presenting a dynamic moving ripple stimulus and then used the responses to construct spectrotemporal receptive fields (STRFs). For each neuron, we constructed three STRFs, one for short-ISI events (ISI < 15 ms); one for isolated, long-ISI events (ISI > 15 ms); and one including all events. To characterize stimulus encoding, we calculated the feature selectivity and event information for each of the STRFs. Short-ISI spikes were more feature selective and conveyed information more efficiently. The different ISI regimens of AI neurons did not represent different stimulus features, but short-ISI spike events did contribute over-proportionately to the full spike train STRF information. Thus short-ISIs constitute a robust representation of auditory features, and they are particularly effective at driving postsynaptic activity. This suggests that short-ISI events are especially suited to provide noise immunity and high-fidelity information transmission in AI.

Case-control study of the association of chronic acid suppression and social determinants of health with COVID-19 infection.

Acid suppressants are widely-used classes of medications linked to increased risks of aerodigestive infections. Prior studies of these medications as potentially reversible risk factors for COVID-19 have been conflicting. We aimed to determine the impact of chronic acid suppression use on COVID-19 infection risk while simultaneously evaluating the influence of social determinants of health to validate known and discover novel risk factors. We assessed the association of chronic acid suppression with incident COVID-19 in a 1:1 case-control study of 900 patients tested across three academic medical centers in California, USA. Medical comorbidities and history of chronic acid suppression use were manually extracted from health records by physicians following a pre-specified protocol. Socio-behavioral factors by geomapping publicly-available data to patient zip codes were incorporated. We identified no evidence to support an association between chronic acid suppression and COVID-19 (adjusted odds ratio 1.04, 95% CI 0.92-1.17, P = 0.515). However, several medical and social features were positive (Latinx ethnicity, BMI ≥ 30, dementia, public transportation use, month of the pandemic) and negative (female sex, concurrent solid tumor, alcohol use disorder) predictors of new infection. These findings demonstrate the value of integrating publicly-available databases with medical data to identify critical features of communicable diseases.

Technique and Tips for Multiplanar Correction of Plantar Plate Repairs in Lesser Metatarsophalangeal Joints.

Plantar plate repairs are challenging procedures because of the small anatomy of the plantar plate. This can make them daunting, time-consuming procedures to perform. Advances in technology, such as interference screws and small suture passers, have created improved technique possibilities to decrease difficulty, correct multiple planes of deformity, create stronger constructs, and improve patient results. The plantar plate repair technique presented in this article includes a dorsal approach with a metatarsal osteotomy, a knotless repair that provides a strong construct to allow patients to protectively bear weight immediately, and can reduce operative time by presenting tips to quickly navigate the procedure. The presented technique allows for detailed correction of all three planes of deformity, maximizing patient results.

Anti-Asian Hate and the Health of Older Asian Individuals.

This qualitative study assesses the association of anti-Asian hate with older Asian individuals' health and the clinician's role in addressing hate incidents.

How to do a 3-minute diabetic foot exam.

This brief exam will help you to quickly detect major risks and prompt you to refer patients to appropriate specialists.

Global hyper-synchronous spontaneous activity in the developing optic tectum.

Studies of patterned spontaneous activity can elucidate how the organization of neural circuits emerges. Using in vivo two-photon Ca(2+) imaging, we studied spatio-temporal patterns of spontaneous activity in the optic tectum of Xenopus tadpoles. We found rhythmic patterns of global synchronous spontaneous activity between neurons, which depends on visual experience and developmental stage. By contrast, synchronous spontaneous activity between non-neuronal cells is mediated more locally. To understand the source of the neuronal spontaneous activity, input to the tectum was systematically removed. Whereas removing input from the visual or mechanosensory system alone had little effect on patterned spontaneous activity, removing input from both systems drastically altered it. These results suggest that either input is sufficient to maintain the intrinsically generated spontaneous activity and that patterned spontaneous activity results from input from multisensory systems. Thus, the amphibian midbrain differs from the mammalian visual system, whose spontaneous activity is controlled by retinal waves.