CycleGAN with mutual information loss constraint generates structurally aligned CT images from functional EIT images.

Electrical impedance tomography (EIT) has been employed in the field of medical imaging due to its cost effectiveness, safety profile and portability, but the images generated are relatively low resolution. To address these limitations, we create a novel method using EIT images to generate high resolution structurally aligned images of lungs like those from CT scans. A way to achieve this transformation is via Cycle generative adversarial networks (CycleGAN), which have demonstrated image-to-image translation capabilities across different modalities. However, a generic implementation yields images which may not be aligned with their input image. To solve this issue, we construct and incorporate a Mutual Information (MI) constraint in CycleGAN to translate functional lung EIT images to structural high resolution CT images. The CycleGAN is first trained on unpaired EIT and CT lung images. Afterwards, we generate CT image pairs from EIT images via CycleGANs constrained with MI loss and without this loss. Finally, through generating these 1560 CT image pairs and then comparing the visual results and quantitative metrics, we show that MI constrained CycleGAN produces more structurally aligned CT images, where Normalised Mutual Information (NMI) is increased to 0.2621+/- 0.0052 versus 0.2600 +/- 0.0066, p<0.0001 for non-MI constrained images. By this process, we simultaneously provide functional and structural information, and potentially enable more detailed assessment of lungs.Clinical Relevance- By establishing a structurally aligning generative process via MI Loss in CycleGAN, this study enables EIT-CT conversion, thereby providing functional and structural images for enhanced lung assessment, from just EIT images.

Global and regional lung function assessment using portable electrical impedance tomography (EIT) system: clinical study.

Recent development of affordable, portable and self-administrable electrical impedance tomography (EIT) system demonstrated the feasibility of using standalone EIT and subject's anthropometrics to predict the gold standard spirometry indicators for lung-function assessment. Compared to spirometry, the system showed the advantage of providing spatial mapping of the spirometry indicators. Nevertheless, the previous study was limited to healthy subjects. Here, we recruited (N=88): 47 lung disease patients and 41 healthy controls to perform simultaneous EIT and spirometry measurements to validate the capabilities of the system. Lung disease patients include 13 interstitial lung disease (ILD), 10 asthma, 8 chronic obstructive pulmonary disease (COPD), 8 bronchiectasis, and 8 with other diseases including left pneumonectomy, lung cancer, lung tumor, lymphangioleiomyomatosis, motor neuron disease, heart failure and bronchiolitis obliterans syndrome. The results showed significant correlation of the predicted global spirometry indicators (p<0.0001) and significant distinguishability between most disease groups and healthy subjects demonstrating the capability of the EIT system in diagnostic screening. Furthermore, the regional mapping of the spirometry indicators is evaluated and shown to be distinct for each disease group, providing an additional dimension for medical professionals to diagnose and monitor lung disease patients.Clinical Relevance- This establishes the significance of EIT-based global and regional indicators for assessing lung function on lung disease patients.

Portable electrical impedance tomography (EIT) system stages non-alcoholic fatty liver disease for potential screening and monitoring at home.

This study demonstrates the feasibility of predicting NAFLD using multi-spectral electrical impedance tomography (EIT), group source separation, constant reference EIT and anthropometric measures. Vibration-controlled Transient Elastography (VCTE) Controlled Attenuated Parameter (CAP; n = 121) and magnetic resonance imaging-proton density fat fraction (MRI-PDFF; n = 34) achieved a sensitivity of 70.9% and specificity of 73.8% with our CAP predicting model and sensitivity of 77.8% and specificity of 80.0% with our MRI-PDFF predicting model. In summary, a portable EIT can be a cost-effective and self-administrable alternative for widespread home-based and community-based diagnostic screening and treatment monitoring of NAFLD.Clinical Relevance- Portable multi-spectral EIT system has the sensitivity and specificity to potentially unlock biomedical imaging in telemedicine for home-based and community-based screening, staging and monitoring for NAFLD.

Electric impedance tomography enables portable and non-invasive approach to screen and monitor chronic kidney disease.

Chronic kidney disease (CKD) is an escalating global health concern, and non-invasive means for early CKD detection is eagerly awaited. Here, we explore the potential of using home-based frequency-difference electrical impedance tomography (fdEIT) to evaluate CKD based on bio-conductivity characteristics. We performed bio-conductivity measurement in vivo paired with standard estimated glomerular filtration rate (eGFR) measurements on a N=126 CKD patients by EIT and traditional blood and urine tests, respectively. We developed an EIT processing pipeline that extracts the kidney regions from EIT images. We further developed a regression model and a CKD classification scheme. Our results showed a significant correlation between EIT-features and eGFR, and the classification scheme shows sensitivity and specificity of 76.2% and 74.6% respectively considering stages 1 and 2 CKD versus stages 3, 4 and 5 CKD. These results suggest the feasibility of EIT to be used as a portable, self-administrated and home-based approach for CKD early diagnostic screening and longitudinal monitoring.Clinical Relevance-The results presented here demonstrates a cost-effective, home-based and self-administrative screening process on chronic kidney disease patients, thereby enhancing the quality and area of possible application of telemedicine. By achieving this, the process presented here can relieve the burden of public health system.

Cross modality generative learning framework for anatomical transitive Magnetic Resonance Imaging (MRI) from Electrical Impedance Tomography (EIT) image.

This paper presents a cross-modality generative learning framework for transitive magnetic resonance imaging (MRI) from electrical impedance tomography (EIT). The proposed framework is aimed at converting low-resolution EIT images to high-resolution wrist MRI images using a cascaded cycle generative adversarial network (CycleGAN) model. This model comprises three main components: the collection of initial EIT from the medical device, the generation of a high-resolution transitive EIT image from the corresponding MRI image for domain adaptation, and the coalescence of two CycleGAN models for cross-modality generation. The initial EIT image was generated at three different frequencies (70 kHz, 140 kHz, and 200 kHz) using a 16-electrode belt. Wrist T1-weighted images were acquired on a 1.5T MRI. A total of 19 normal volunteers were imaged using both EIT and MRI, which resulted in 713 paired EIT and MRI images. The cascaded CycleGAN, end-to-end CycleGAN, and Pix2Pix models were trained and tested on the same cohort. The proposed method achieved the highest accuracy in bone detection, with 0.97 for the proposed cascaded CycleGAN, 0.68 for end-to-end CycleGAN, and 0.70 for the Pix2Pix model. Visual inspection showed that the proposed method reduced bone-related errors in the MRI-style anatomical reference compared with end-to-end CycleGAN and Pix2Pix. Multifrequency EIT inputs reduced the testing normalized root mean squared error of MRI-style anatomical reference from 67.9% ± 12.7% to 61.4% ± 8.8% compared with that of single-frequency EIT. The mean conductivity values of fat and bone from regularized EIT were 0.0435 ± 0.0379 S/m and 0.0183 ± 0.0154 S/m, respectively, when the anatomical prior was employed. These results demonstrate that the proposed framework is able to generate MRI-style anatomical references from EIT images with a good degree of accuracy.

Functional MRI reveals brain-wide actions of thalamically-initiated oscillatory activities on associative memory consolidation.

As a key oscillatory activity in the brain, thalamic spindle activities are long believed to support memory consolidation. However, their propagation characteristics and causal actions at systems level remain unclear. Using functional MRI (fMRI) and electrophysiology recordings in male rats, we found that optogenetically-evoked somatosensory thalamic spindle-like activities targeted numerous sensorimotor (cortex, thalamus, brainstem and basal ganglia) and non-sensorimotor limbic regions (cortex, amygdala, and hippocampus) in a stimulation frequency- and length-dependent manner. Thalamic stimulation at slow spindle frequency (8 Hz) and long spindle length (3 s) evoked the most robust brain-wide cross-modal activities. Behaviorally, evoking these global cross-modal activities during memory consolidation improved visual-somatosensory associative memory performance. More importantly, parallel visual fMRI experiments uncovered response potentiation in brain-wide sensorimotor and limbic integrative regions, especially superior colliculus, periaqueductal gray, and insular, retrosplenial and frontal cortices. Our study directly reveals that thalamic spindle activities propagate in a spatiotemporally specific manner and that they consolidate associative memory by strengthening multi-target memory representation.

Hippocampus Modulates Vocalizations Responses at Early Auditory Centers.

Despite its prominence in learning and memory, hippocampal influence in early auditory processing centers remains unknown. Here, we examined how hippocampal activity modulates sound-evoked responses in the auditory midbrain and thalamus using optogenetics and functional MRI (fMRI) in rodents. Ventral hippocampus (vHP) excitatory neuron stimulation at 5 Hz evoked robust hippocampal activity that propagates to the primary auditory cortex. We then tested 5 Hz vHP stimulation paired with either natural vocalizations or artificial/noise acoustic stimuli. vHP stimulation enhanced auditory responses to vocalizations (with a negative or positive valence) in the inferior colliculus, medial geniculate body, and auditory cortex, but not to their temporally reversed counterparts (artificial sounds) or broadband noise. Meanwhile, pharmacological vHP inactivation diminished response selectivity to vocalizations. These results directly reveal the large-scale hippocampal participation in natural sound processing at early centers of the ascending auditory pathway. They expand our present understanding of hippocampus in global auditory networks.

Affordable, portable and self-administrable electrical impedance tomography enables global and regional lung function assessment.

Accessibility of diagnostic screening and treatment monitoring devices for respiratory diseases is critical in promoting healthcare and reducing sudden complications and mortality. Spirometry is the standard for diagnosing and monitoring several lung diseases. However, it lacks regional assessment capabilities necessary for detecting subtle regional changes in certain diseases. It also requires challenging breathing maneuvers difficult for elderlies, children, and diseased patients. Here, we actualized an affordable, portable, and self-administrable electrical impedance tomography (EIT) system for home-based lung function assessment and telemedicine. Through simultaneous EIT-spirometry trials on healthy subjects, we demonstrated that our device can predict spirometry indicators over a wide range and can provide regional mapping of these indicators. We further developed a close-to-effortless breathing paradigm and tested it by longitudinally monitoring a COVID-19 discharged subject and two healthy controls with results suggesting the paradigm can detect initial deterioration followed by recovery. Overall, the EIT system can be widely applicable for lung function screening and monitoring both at homes and clinics.

Standalone electrical impedance tomography predicts spirometry indicators and enables regional lung assessment.

Electrical impedance tomography (EIT) is a bio-medical imaging modality that has several clinical applications namely for human lungs. Yet, its relationship with gold standard lung diagnostic tools including spirometry is not available. In this study, simultaneous EIT and spirometry measurements were collected for 14 healthy subjects who performed forced breathing paradigms of different efforts simulating a wide range of spirometry indicators. It is demonstrated that EIT can predict standard spirometry indicators over a wide dynamic range, with a potential sensitivity and specificity of 98% and 100%, respectively, in detecting obstructive patterns. It is also shown that EIT can provide a regional mapping of the spirometry indicator which are shown to be consistent with their corresponding global indicators. Overall, EIT can predict spirometry indicators and can assess regional lung health through parametric mapping. Clinical Relevance- This study shows that EIT can infer standard spirometry indicators and potentially assess regional lung health. Therefore, EIT can be used for screening, diagnosis, and monitoring of obstructive and resistive lung diseases.

Bio-conductivity characteristics of chronic kidney disease stages examined by portable frequency-difference electrical impedance tomography.

Chronic kidney disease (CKD) is an escalating global health concern, and non-invasive means for early CKD detection is eagerly awaited. Here, we explore the potential of using home-based frequency-difference electrical impedance tomography (fdEIT) to evaluate CKD based on bio-conductivity characteristics. We first verified the feasibility of using portable EIT capturing bio-conductivity in fresh pig kidneys ex vivo. We further performed bio-conductivity measurement in vivo paired with standard eGFR measurements on CKD patients by EIT and traditional blood test, respectively. Our results showed a significant correlation between renal bio-conductivity changes captured by fdEIT and standard eGFR scores. These results hold promise to be developed into a non-invasive and portable device for early CKD detection and longitudinal CKD treatment monitoring in clinical, community and home-based settings. Clinical Relevance - A novel non-invasive bio-conductivity approach was developed for CKD classification. The renal assessment with portable EIT device demonstrated the potential to ameliorate the detection and classification of CKD into a portable, accessible, self-administrable home-based process.

Unmixing multi-spectral electrical impedance tomography (EIT) predicts clinical-standard controlled attenuation parameter (CAP) for nonalcoholic fatty liver disease classification: a feasibility study.

Here, we tested the feasibility of predicting CAP with multi-spectral EIT. Conductivity and CAP were acquired from nonalcoholic fatty liver disease patients using a portable EIT system and vibration-controlled transient elastography (VCTE). We then used frequency-difference conductivity and waist-over-height as prediction features to estimate CAP and found an adj. R2 of 0.92. We further developed a novel prediction method by incorporating EIT spectral unmixing reconstruction and demonstrated an improvement in CAP estimation. Last, we optimized the EIT acquisition process by minimizing the total variance of the CAP estimator. Clinical Relevance: EIT can estimate clinical-standard liver disease classification. This portable EIT system is potentially cost-effective and self-administrable with short acquisition time (3 mins), while VCTE are costly and usually requires a trained personnel to operate with longer acquisition time (5-10 mins).

COVID-19 death and kidney disease in a multiracial Asian country.

INTRODUCTION: COVID-19 infection and kidney disease (KD) carry a considerable risk of mortality. Understanding predictors of death and KD may help improve management and patient outcome. METHODS: This is a prospective multicentre observational study conducted in a multiracial Asian country to identify predictors of death and acute kidney injury (AKI) in hospitalized COVID-19 patients from January to June 2020. RESULTS: A total of 6078 patients were included in this study. Mean age was 37.3 (±16.8) years, 71% were male, 59.4% Malay, 6.7% Chinese, 2.3% Indian and 31.7% other ethnicities. AKI was seen in 3.5% of patients while 1.6% had pre-existing chronic kidney disease (CKD). Overall case fatality rate (CFR) was 1.3%. Patients with KD (AKI and CKD) had CFR of 20%. Many factors were associated with increased risk of death and AKI. However, significant predictors of death after adjustment for covariates were age (>70 years), Chinese ethnicity, diabetes mellitus (DM) and KD. Adjusted predictors of AKI were age (>51 years), DM and severity at presentation. Chinese were 2.58 times more likely to die (p = .036) compared to Malay. Centre capacity to manage, ventilate and dialyze patients significantly influenced death. Among those with AKI, the most common symptoms were fever, cough, and dyspnea. They had lower absolute lymphocyte count, were more likely to be admitted to ICU, required more ventilation and longer hospitalization. CONCLUSION: Patient and centre factors influence death and AKI among COVID-19 patients. This study also demonstrates death disparities across different racial groups and centre capacities in this multiracial Asian country.

Neural activity temporal pattern dictates long-range propagation targets.

Brain possesses a complex spatiotemporal architecture for efficient information processing and computing. However, it remains unknown how neural signal propagates to its intended targets brain-wide. Using optogenetics and functional MRI, we arbitrarily initiated various discrete neural activity pulse trains with different temporal patterns and revealed their distinct long-range propagation targets within the well-defined, topographically organized somatosensory thalamo-cortical circuit. We further observed that such neural activity propagation over long range could modulate brain-wide sensory functions. Electrophysiological analysis indicated that distinct propagation pathways arose from system level neural adaptation and facilitation in response to the neural activity temporal characteristics. Together, our findings provide fundamental insights into the long-range information transfer and processing. They directly support that temporal coding underpins the whole brain functional architecture in presence of the vast and relatively static anatomical architecture.

Functional magnetic resonance imaging of enhanced central auditory gain and electrophysiological correlates in a behavioral model of hyperacusis.

Hyperacusis is a debilitating hearing condition in which normal everyday sounds are perceived as exceedingly loud, annoying, aversive or even painful. The prevalence of hyperacusis approaches 10%, making it an important, but understudied medical condition. To noninvasively identify the neural correlates of hyperacusis in an animal model, we used sound-evoked functional magnetic resonance imaging (fMRI) to locate regions of abnormal activity in the central nervous system of rats with behavioral evidence of hyperacusis induced with an ototoxic drug (sodium salicylate, 250 mg/kg, i.p.). Reaction time-intensity measures of loudness-growth revealed behavioral evidence of salicylate-induced hyperacusis at high intensities. fMRI revealed significantly enhanced sound-evoked responses in the auditory cortex (AC) to 80 dB SPL tone bursts presented at 8 and 16 kHz. Sound-evoked responses in the inferior colliculus (IC) were also enhanced, but to a lesser extent. To confirm the main results, electrophysiological recordings of spike discharges from multi-unit clusters were obtained from the central auditory pathway. Salicylate significantly enhanced tone-evoked spike-discharges from multi-unit clusters in the AC from 4 to 30 kHz at intensities ≥60 dB SPL; less enhancement occurred in the medial geniculate body (MGB), and even less in the IC. Our results demonstrate for the first time that non-invasive sound-evoked fMRI can be used to identify regions of neural hyperactivity throughout the brain in an animal model of hyperacusis.

Reduction of sound-evoked midbrain responses observed by functional magnetic resonance imaging following acute acoustic noise exposure.

Short duration and high intensity acoustic exposures can lead to temporary hearing loss and auditory nerve degeneration. This study investigates central auditory system function following such acute exposures after hearing loss recedes. Adult rats were exposed to 100 dB sound pressure level noise for 15 min. Auditory brainstem responses (ABRs) were recorded with click sounds to check hearing thresholds. Functional magnetic resonance imaging (fMRI) was performed with tonal stimulation at 12 and 20 kHz to investigate central auditory changes. Measurements were performed before exposure (0D), 7 days after (7D), and 14 days after (14D). ABRs show an ∼6 dB threshold shift shortly after exposure, but no significant threshold differences between 0D, 7D, and 14D. fMRI responses are observed in the lateral lemniscus (LL) and inferior colliculus (IC) of the midbrain. In the IC, responses to 12 kHz are 3.1 ± 0.3% (0D), 1.9 ± 0.3% (7D), and 2.9 ± 0.3% (14D) above the baseline magnetic resonance imaging signal. Responses to 20 kHz are 2.0 ± 0.2% (0D), 1.4 ± 0.2% (7D), and 2.1 ± 0.2% (14D). For both tones, responses at 7D are less than those at 0D (p < 0.01) and 14D (p < 0.05). In the LL, similar trends are observed. Acute exposure leads to functional changes in the auditory midbrain with timescale of weeks.

Maternal knowledge and attitudes to universal newborn hearing screening: Reviewing an established program.

OBJECTIVES: To facilitate early diagnosis of infants with hearing loss, a universal newborn hearing screening program (UNHS) has been implemented in Hong Kong's public hospitals for over a decade. However, there have been no known studies investigating parent attitudes to, and satisfaction with, UNHS since its launch in Hong Kong. The present study aimed to investigate knowledge of UNHS as well as infant hearing development, and attitudes and satisfaction with UNHS, in Hong Kong mothers with newborns. The study was designed to help evaluate and improve an established UNHS public hospital program, based on the perspectives of service users. METHODS: A researcher-developed questionnaire was administered to 102 mothers whose newborn had received UNHS in the postnatal wards of a large public hospital in Hong Kong. The questionnaire considered parental knowledge of UNHS and infant hearing development, attitudes and satisfaction toward public hospital UNHS. In the knowledge dimension, parents' preferred time and location for pre-test information delivery, interpretation of screening results, and knowledge of hearing developmental milestones were surveyed. In addition, maternal attitudes to and satisfaction with UNHS screening services, the potential impact of UNHS on parent emotions and parent-baby bonding, attitudes toward informed consent, and willingness to comply with diagnostic assessment referral were also be surveyed. RESULTS: Mean participant scores on knowledge of infant hearing development were relatively low (M = 2.59/6.0, SD = 0.90). Many mothers also underestimated the potential ongoing risks of hearing impairment in babies. Around 80% of mothers thought an infant could not have hearing impairment after passing the screening. In addition, one-third of mothers thought a baby could not later develop hearing impairment in infancy or childhood. In terms of attitudes and satisfaction, participants gave somewhat negative ratings for questions regarding receiving sufficient information about the screening (M = 2.90/5.0, SD = 1.27), screening procedure (M = 2.20/5.0, SD = 1.08), and sufficiency of information about results (M = 2.87/5.0, SD = 1.14). Nonetheless, participants gave positive ratings concerning whether screening could lead to early diagnosis (M = 4.61/5.0, SD = 0.57) and over 95% of mothers supported UNHS despite potential for false positive results. Mothers reported a high willingness to bring their baby to follow-up assessments if required (M = 4.53/5.0, SD = 0.56). Participants gave positive ratings for their level of satisfaction with the time and location of first UNHS information provision (M = 4.34/5.0, SD = 0.80) and the way permission was asked for screening the baby (M = 4.04/5.0, SD = 0.97) but alternative procedures were also recommended. Most recommendations focused on providing more information about the test and a more detailed explanation of screening results. CONCLUSIONS: The survey results highlighted the need to provide more information to parents about infant hearing development to support home monitoring for signs of hearing loss after UNHS, as well as more detailed explanation and information regarding hearing screening and the implications of results to parents. Regardless of location, surveys of this type may provide valuable support for UNHS program quality assurance.

Low-frequency hippocampal-cortical activity drives brain-wide resting-state functional MRI connectivity.

The hippocampus, including the dorsal dentate gyrus (dDG), and cortex engage in bidirectional communication. We propose that low-frequency activity in hippocampal-cortical pathways contributes to brain-wide resting-state connectivity to integrate sensory information. Using optogenetic stimulation and brain-wide fMRI and resting-state fMRI (rsfMRI), we determined the large-scale effects of spatiotemporal-specific downstream propagation of hippocampal activity. Low-frequency (1 Hz), but not high-frequency (40 Hz), stimulation of dDG excitatory neurons evoked robust cortical and subcortical brain-wide fMRI responses. More importantly, it enhanced interhemispheric rsfMRI connectivity in various cortices and hippocampus. Subsequent local field potential recordings revealed an increase in slow oscillations in dorsal hippocampus and visual cortex, interhemispheric visual cortical connectivity, and hippocampal-cortical connectivity. Meanwhile, pharmacological inactivation of dDG neurons decreased interhemispheric rsfMRI connectivity. Functionally, visually evoked fMRI responses in visual regions also increased during and after low-frequency dDG stimulation. Together, our results indicate that low-frequency activity robustly propagates in the dorsal hippocampal-cortical pathway, drives interhemispheric cortical rsfMRI connectivity, and mediates visual processing.

The multi-level impact of chronic intermittent hypoxia on central auditory processing.

During hypoxia, the tissues do not obtain adequate oxygen. Chronic hypoxia can lead to many health problems. A relatively common cause of chronic hypoxia is sleep apnea. Sleep apnea is a sleep breathing disorder that affects 3-7% of the population. During sleep, the patient's breathing starts and stops. This can lead to hypertension, attention deficits, and hearing disorders. In this study, we apply an established chronic intermittent hypoxemia (CIH) model of sleep apnea to study its impact on auditory processing. Adult rats were reared for seven days during sleeping hours in a gas chamber with oxygen level cycled between 10% and 21% (normal atmosphere) every 90s. During awake hours, the subjects were housed in standard conditions with normal atmosphere. CIH treatment significantly reduces arterial oxygen partial pressure and oxygen saturation during sleeping hours (relative to controls). After treatment, subjects underwent functional magnetic resonance imaging (fMRI) with broadband sound stimulation. Responses are observed in major auditory centers in all subjects, including the auditory cortex (AC) and auditory midbrain. fMRI signals from the AC are statistically significantly increased after CIH by 0.13% in the contralateral hemisphere and 0.10% in the ipsilateral hemisphere. In contrast, signals from the lateral lemniscus of the midbrain are significantly reduced by 0.39%. Signals from the neighboring inferior colliculus of the midbrain are relatively unaffected. Chronic hypoxia affects multiple levels of the auditory system and these changes are likely related to hearing disorders associated with sleep apnea.

Improving newborn hearing screening: Are automated auditory brainstem response ear inserts an effective option?

OBJECTIVE: Universal newborn hearing screening is an established practice among Hong Kong public hospitals using a 2-stage automated auditory brainstem response (AABR) screening protocol. To enhance overall efficiency without sacrificing program accuracy, cost reduction in terms of replacing the initial ear coupler-based screening with a more economical ear insert-based screening procedure was considered. This study examined the utility of an insert-based AABR initial screening approach and the projected cost-effectiveness of a combined probe-based plus follow-up ear coupler AABR screening procedure. METHODS: Following prenatal maternal consent, newborn hearing screening was conducted with 167 healthy neonates using a cross-sectional, repeated measures study design. The neonates were screened with AABR sequentially; using ear coupler and ear probe (insert) procedures, in both ears, with two different but comparable AABR instruments. Testing took place in the antenatal ward of a department of obstetrics and gynaecology, at a large public hospital. RESULTS: With the specific combination of instruments deployed for this study insert-based AABR screening generated a five-fold higher rescreen rate and took an additional 50% screening time compared to coupler-based AABR screening. Although the cost of consumables used in a 2-stage AABR screening protocol would reduce by 9.87% if the combined procedure was implemented, the findings indicated AABR screening when conducted with an ear probe has reduced utility compared with conventional ear coupler screening. CONCLUSIONS: Significant differences may occur in screening outcomes when changes are made to coupler method. Initiating a 2-stage AABR screening protocol with an ear insert technique may be impracticable in newborn nurseries given the greater number of false positive cases generated by this approach in the present study and the increased time required to carry out an insert-based procedure.

Structures of eukaryotic ribosomal stalk proteins and its complex with trichosanthin, and their implications in recruiting ribosome-inactivating proteins to the ribosomes.

Ribosome-inactivating proteins (RIP) are RNA N-glycosidases that inactivate ribosomes by specifically depurinating a conserved adenine residue at the α-sarcin/ricin loop of 28S rRNA. Recent studies have pointed to the involvement of the C-terminal domain of the eukaryotic stalk proteins in facilitating the toxic action of RIPs. This review highlights how structural studies of eukaryotic stalk proteins provide insights into the recruitment of RIPs to the ribosomes. Since the C-terminal domain of eukaryotic stalk proteins is involved in specific recognition of elongation factors and some eukaryote-specific RIPs (e.g., trichosanthin and ricin), we postulate that these RIPs may have evolved to hijack the translation-factor-recruiting function of ribosomal stalk in reaching their target site of rRNA.