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BioRxiv : the Preprint Server For... Jun 2024The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to...
The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to differences in the types and numbers of low-voltage-gated potassium channels found in the neurons' membranes. Expression for some low-voltage gated ion channels like KCNQ4 is upregulated during early post-natal development; suggesting that ion channel composition and neuronal diversity may be shaped by hair cell activity. This idea is consistent with recent work showing that glutamatergic input from hair cells is necessary for the normal diversification auditory neurons. To test if biophysical diversity is similarly dependent on glutamatergic input in vestibular neurons, we examined the maturation of the vestibular epithelium and ganglion neurons in mice whose hair cell synapses lack glutamate. Despite lacking glutamatergic input, the knockout mice showed no notable balance deficits and crossed challenging balance beams with little difficulty. Immunolabeling of the vestibular epithelia showed normal development as indicated by an identifiable striolar zone with calyceal terminals labeled by molecular marker calretinin, and normal expression of KCNQ4 by the end of the second post-natal week. We found similar numbers of Type I and Type II hair cells in the knockout and wildtype animals, regardless of epithelial zone. Thus, the presumably quiescent Type II hair cells are not cleared from the epithelium. Patch-clamp recordings showed that biophysical diversity of vestibular ganglion neurons in the mice is comparable to that found in wildtype controls, with a similar range firing patterns at both immature and juvenile ages. However, our results suggest a subtle biophysical alteration to the largest ganglion cells (putative somata of central zone afferents); those in the knockout had smaller net conductance and were more excitable than those in the wild type. Thus, unlike in the auditory nerve, glutamatergic signaling is unnecessary for producing biophysical diversity in vestibular ganglion neurons. And yet, because the input signals from vestibular hair cells are complex and not solely reliant on quantal release of glutamate, whether diversity of vestibular ganglion neurons is simply hardwired or regulated by a more complex set of input signals remains to be determined.
PubMed: 38915604
DOI: 10.1101/2024.06.12.597464 -
The Indian Journal of Radiology &... Jul 2024Although abundant literature is currently available on the use of deep learning for breast cancer detection in mammography, the quality of such literature is widely... (Review)
Review
Although abundant literature is currently available on the use of deep learning for breast cancer detection in mammography, the quality of such literature is widely variable. To evaluate published literature on breast cancer detection in mammography for reproducibility and to ascertain best practices for model design. The PubMed and Scopus databases were searched to identify records that described the use of deep learning to detect lesions or classify images into cancer or noncancer. A modification of Quality Assessment of Diagnostic Accuracy Studies (mQUADAS-2) tool was developed for this review and was applied to the included studies. Results of reported studies (area under curve [AUC] of receiver operator curve [ROC] curve, sensitivity, specificity) were recorded. A total of 12,123 records were screened, of which 107 fit the inclusion criteria. Training and test datasets, key idea behind model architecture, and results were recorded for these studies. Based on mQUADAS-2 assessment, 103 studies had high risk of bias due to nonrepresentative patient selection. Four studies were of adequate quality, of which three trained their own model, and one used a commercial network. Ensemble models were used in two of these. Common strategies used for model training included patch classifiers, image classification networks (ResNet in 67%), and object detection networks (RetinaNet in 67%). The highest reported AUC was 0.927 ± 0.008 on a screening dataset, while it reached 0.945 (0.919-0.968) on an enriched subset. Higher values of AUC (0.955) and specificity (98.5%) were reached when combined radiologist and Artificial Intelligence readings were used than either of them alone. None of the studies provided explainability beyond localization accuracy. None of the studies have studied interaction between AI and radiologist in a real world setting. While deep learning holds much promise in mammography interpretation, evaluation in a reproducible clinical setting and explainable networks are the need of the hour.
PubMed: 38912238
DOI: 10.1055/s-0043-1775737 -
The Journal of Clinical and Aesthetic... Jun 2024Patch testing is the standard diagnostic test used for patients presenting with symptoms of allergic contact dermatitis. The grading of patch test results classically...
Patch testing is the standard diagnostic test used for patients presenting with symptoms of allergic contact dermatitis. The grading of patch test results classically varies from 1 to 3. The assessment of these results begins with a visual inspection of the presence of erythema, vesiculation, and induration. This leads to a subjectivity in visual evaluation of a patch test. Positive patch testing results can present differently in patients with darker skin tones. A greater variety of images of allergic contact dermatitis in patients with darker skin phototypes can better guide the diagnosis of this condition in skin of color. People with darker phototypes are historically underrepresented in dermatologic images and texts; thus, identifying erythema in darker phototypes may be more difficult for dermatologists, whether or not they were trained in areas of decreased phototype diversity. In this article, we present positive patch testing findings on several different phototypes, with the intention of contributing to images of phototypes underrepresented in dermatology literature.
PubMed: 38912195
DOI: No ID Found -
Vision Research Jun 2024Short-term monocular deprivation in normally sighted adult humans produces a transient shift of ocular dominance, boosting the deprived eye. This effect has been...
Short-term monocular deprivation in normally sighted adult humans produces a transient shift of ocular dominance, boosting the deprived eye. This effect has been documented with both perceptual tests and through physiological recordings, but no previous study simultaneously measured physiological responses and the perceptual effects of deprivation. Here we propose an integrated experimental paradigm that combines binocular rivalry with pupillometry, to introduce an objective physiological index of ocular dominance plasticity, acquired concurrently with perceptual testing. Ten participants reported the perceptual dynamics of binocular rivalry, while we measured pupil diameter. Stimuli were a white and a black disk, each presented monocularly. Rivalry dynamics and pupil-size traces were compared before and after 2 h of monocular deprivation, achieved by applying a translucent patch over the dominant eye. Consistent with prior research, we observed that monocular deprivation boosts the deprived-eye signal and consequently increases ocular dominance. In line with previous studies, we also observed subtle but systematic modulations of pupil size that tracked alternations between exclusive dominance phases of the black or white disk. Following monocular deprivation, the amplitude of these pupil-size modulations increased, which is consistent with the post-deprivation boost of the deprived eye and the increase of ocular dominance. This provides evidence that deprivation impacts the effective strength of monocular visual stimuli, coherently affecting perceptual reports and the automatic and unconscious regulation of pupil diameter. Our results show that a combined paradigm of binocular rivalry and pupillometry gives new insights into the physiological mechanisms underlying deprivation effects.
PubMed: 38909478
DOI: 10.1016/j.visres.2024.108449 -
Journal of Medical Case Reports Jun 2024Granuloma annulare is a noninfectious inflammatory granulomatous skin disease characterized by an erythematous or skin colored annulare plaque. The diagnosis of...
BACKGROUND
Granuloma annulare is a noninfectious inflammatory granulomatous skin disease characterized by an erythematous or skin colored annulare plaque. The diagnosis of granuloma annulare may be challenging owing to its diverse morphology. In such cases, a correlation between the clinical findings and histologic findings are necessary.
CASE PRESENTATION
We report a case of granuloma annulare after purified protein derivative administration. A 56-year-old Caucasian female patient complained of mildly pruritic rashes which started on both arms and lower extremities, and eventually spread to both thighs, the left popliteal region, left upper back, and the right abdominal area. About 6 weeks prior to the eruption of the rashes, the patient had been given a purified protein derivative tuberculin skin test. Biopsy specimens revealed dermal histiocytes palisading around areas of mucin and degenerated collagen, confirming granuloma annulare. After treatment with 0.1% topical triamcinolone acetanide and 500 mg oral metronidazole, the patient's lesions resolved.
DISCUSSION
Relatively little is known about granuloma annulare's exact etiology. Granuloma annulare has four variations presenting as either localized, generalized, subcutaneous, or perforating and patch granuloma annulare. The clinical prognosis for granuloma annulare varies according to clinical subtypes. Proposed causal mechanisms of subcutaneous granuloma annulare include physical trauma, infections, immunizations, insect bites, diabetes mellitus, and alterations in the cell-mediated immune responses. The disease likely has an inflammatory component. Clinically, granuloma annulare may be confused with many other skin diseases.
CONCLUSION
This case of subcutaneous granuloma annulare was reported since it is a rare dermatologic pathological condition that can be confused with other skin rash disorders. Although it is a benign self-limited disease, definitive diagnosis is important to rule out other pathologies with similar clinical appearances, such as cancer or human immunodeficiency virus (HIV) infection. Diagnostic confirmation is best made through skin biopsy.
Topics: Humans; Granuloma Annulare; Female; Middle Aged; Treatment Outcome
PubMed: 38902812
DOI: 10.1186/s13256-024-04598-w -
Cureus May 2024As globalization progresses, cases of sickle cell disease (SCD) are now being seen even in Japan, where SCD did not originally exist. SCD causes not only anemia but also...
As globalization progresses, cases of sickle cell disease (SCD) are now being seen even in Japan, where SCD did not originally exist. SCD causes not only anemia but also peripheral blood flow obstruction, which can lead to systemic complications. This report represents a case of sickle cell retinopathy (SCR) in Japan discovered with the onset of retinal artery occlusion (RAO). The patient, a 20-year-old African-Japanese male, was being monitored for SCD at the Nagoya University Hospital, Pediatrics Department, Nagoya, Japan. Following a chest pain episode, he reported a loss of vision in his right eye and was referred to the ophthalmology department. Examination showed reduced visual acuity in the right eye 20/40 compared to the left 20/20. A Goldman visual field test indicated central vision loss in the right eye, and fundoscopic examination revealed yellow-white lesions centered on the macula and peripheral salmon-patch-like lesions in the right eye, with peripheral black sunburst-like lesions in the left eye. Optical coherence tomography (OCT) of the right eye showed inner retinal edema within the macula, suggesting an SCR accompanied by branch RAO. Six months later, he complained of further vision loss in his right eye. Examination and OCT revealed sub-inner limiting membrane hemorrhage in the right eye, suggesting worsening of the SCR. SCD is exceedingly rare among native Japanese but is likely to be encountered more frequently as globalization progresses. Even in countries where SCD has traditionally been rare, attention must be paid to the occurrence of severe SCR when managing SCD.
PubMed: 38899256
DOI: 10.7759/cureus.60653 -
Lakartidningen Jun 2024In the armed forces, marching still remains a major component in the training of the young recruits. In the following we describe a young recruit who, following...
In the armed forces, marching still remains a major component in the training of the young recruits. In the following we describe a young recruit who, following instructions, prophylactically used adhesives to prevent chafing. The recruit developed an allergic contact dermatitis with generalized spreading. The adhesive products recommended are sold on a global market and are extensively used. Allergic contact dermatitis from these products have so far only been reported from Sweden. Unfortunately, even though the first cases were reported some years ago, new cases are still diagnosed. When medical devices are recommended to be used on the skin for a prolonged time and under extreme conditions, sensitization and a subsequent allergic contact dermatitis must be considered.
Topics: Humans; Dermatitis, Allergic Contact; Dermatitis, Occupational; Military Personnel; Male; Adhesives; Patch Tests; Young Adult
PubMed: 38896037
DOI: No ID Found -
BioRxiv : the Preprint Server For... Jun 2024Premature infants often experience frequent hypoxic episodes due to immaturity of respiratory control that may result in disturbances of gray and white matter...
BACKGROUND
Premature infants often experience frequent hypoxic episodes due to immaturity of respiratory control that may result in disturbances of gray and white matter development and long-term cognitive and behavioral abnormalities. We hypothesize that neonatal intermittent hypoxia alters cortical maturation of excitatory and inhibitory circuits that can be detected early with functional MRI.
METHODS
C57BL/6 mouse pups were exposed to an intermittent hypoxia (IH) regimen consisting of 12 to 20 daily hypoxic episodes of 5% oxygen exposure for 2 min at 37C from P3 to P7, followed by MRI at P12 and electrophysiological recordings in cortical slices and in vivo at several time points between P7 and P13. Behavioral tests were conducted at P41-P50 to assess animal activity and motor learning.
RESULTS
Adult mice after neonatal IH exhibited hyperactivity in open field test and impaired motor learning in complex wheel tasks. Patch clamp and evoked field potential electrophysiology revealed increased glutamatergic transmission accompanied by elevation of tonic inhibition. A decreased synaptic inhibitory drive was evidenced by miniature IPSC frequency on pyramidal cells, multi-unit activity recording in vivo in the motor cortex with selective GABA receptor inhibitor picrotoxin injection, as well as by the decreased interneuron density at P13. There was also an increased tonic depolarizing effect of picrotoxin after IH on principal cells' membrane potential on patch clamp and direct current potential in extracellular recordings. The amplitude of low-frequency fluctuation on resting-state fMRI was larger, with a larger increase after picrotoxin injection in the IH group.
CONCLUSIONS
Increased excitatory glutamatergic transmission, decreased numbers, and activity of inhibitory interneurons after neonatal IH may affect the maturation of connectivity in cortical networks, resulting in long-term cognitive and behavioral changes, including impaired motor learning and hyperactivity. Functional MRI reveals increased intrinsic connectivity in the sensorimotor cortex, suggesting neuronal dysfunction in cortical maturation after neonatal IH. The increased tonic inhibition, presumably due to tonic extrasynaptic GABA receptor drive, may be compensatory to the elevated excitatory glutamatergic transmission.
PubMed: 38895332
DOI: 10.1101/2024.06.04.596449 -
BioRxiv : the Preprint Server For... Jun 2024Human and mouse dorsal root ganglia (hDRG and mDRG) neurons are important tools in understanding the molecular and electrophysiological mechanisms that underlie...
Human and mouse dorsal root ganglia (hDRG and mDRG) neurons are important tools in understanding the molecular and electrophysiological mechanisms that underlie nociception and drive pain behaviors. One of the simplest differences in firing phenotypes is that neurons are single-firing (exhibit only one action potential) or multi-firing (exhibit 2 or more action potentials). To determine if single- and multi-firing hDRG exhibit differences in intrinsic properties, firing phenotypes, and AP waveform properties, and if these properties could be used to predict multi-firing, we measured 22 electrophysiological properties by whole-cell patch-clamp electrophysiology of 94 hDRG neurons from 6 male and 4 female donors. We then analyzed the data using several machine learning models to determine if these properties could be used to predict multi-firing. We used 1000 iterations of Monte Carlo Cross Validation to split the data into different train and test sets and tested the Logistic Regression, k-Nearest Neighbors, Random Forest, Supported Vector Classification, and XGBoost machine learning models. All models tested had a greater than 80% accuracy on average, with Supported Vector Classification and XGBoost performing the best. We found that several properties correlated with multi-firing hDRG neurons and together could be used to predict multi-firing neurons in hDRG including a long decay time, a low rheobase, and long first spike latency. We also found that the hDRG models were able to predict multi-firing with 90% accuracy in mDRG. Targeting the neuronal properties that lead to multi-firing could elucidate better targets for treatment of chronic pain.
PubMed: 38895314
DOI: 10.1101/2024.06.03.597213 -
Investigative Ophthalmology & Visual... Jun 2024We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
PURPOSE
We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
METHODS
Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed.
RESULTS
At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]).
CONCLUSIONS
Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.
Topics: Humans; Male; Female; Adult; Prospective Studies; Tomography, Optical Coherence; Visual Acuity; Middle Aged; Electroretinography; Myosin VIIa; Visual Fields; Young Adult; Adolescent; Usher Syndromes; Genetic Therapy; Child; Visual Field Tests; Europe; Fluorescein Angiography; Follow-Up Studies; Aged; Longitudinal Studies; Disease Progression; Myosins; Retina
PubMed: 38884554
DOI: 10.1167/iovs.65.6.25