Brain Wearables: Validation Toolkit for Ear-Level EEG Sensors.

EEG-enabled earbuds represent a promising frontier in brain activity monitoring beyond traditional laboratory testing. Their discrete form factor and proximity to the brain make them the ideal candidate for the first generation of discrete non-invasive brain-computer interfaces (BCIs). However, this new technology will require comprehensive characterization before we see widespread consumer and health-related usage. To address this need, we developed a validation toolkit that aims to facilitate and expand the assessment of ear-EEG devices. The first component of this toolkit is a desktop application ("EaR-P Lab") that controls several EEG validation paradigms. This application uses the Lab Streaming Layer (LSL) protocol, making it compatible with most current EEG systems. The second element of the toolkit introduces an adaptation of the phantom evaluation concept to the domain of ear-EEGs. Specifically, it utilizes 3D scans of the test subjects' ears to simulate typical EEG activity around and inside the ear, allowing for controlled assessment of different ear-EEG form factors and sensor configurations. Each of the EEG paradigms were validated using wet-electrode ear-EEG recordings and benchmarked against scalp-EEG measurements. The ear-EEG phantom was successful in acquiring performance metrics for hardware characterization, revealing differences in performance based on electrode location. This information was leveraged to optimize the electrode reference configuration, resulting in increased auditory steady-state response (ASSR) power. Through this work, an ear-EEG evaluation toolkit is made available with the intention to facilitate the systematic assessment of novel ear-EEG devices from hardware to neural signal acquisition.

How Do We Allocate Our Resources When Listening and Memorizing Speech in Noise? A Pupillometry Study.

OBJECTIVES: Actively following a conversation can be demanding and limited cognitive resources must be allocated to the processing of speech, retaining and encoding the perceived content, and preparing an answer. The aim of the present study was to disentangle the allocation of effort into the effort required for listening (listening effort) and the effort required for retention (memory effort) by means of pupil dilation. DESIGN: Twenty-five normal-hearing German speaking participants underwent a sentence final word identification and recall test, while pupillometry was conducted. The participants' task was to listen to a sentence in four-talker babble background noise and to repeat the final word afterward. At the end of a list of sentences, they were asked to recall as many of the final words as possible. Pupil dilation was recorded during different list lengths (three sentences versus six sentences) and varying memory load (recall versus no recall). Additionally, the effect of a noise reduction algorithm on performance, listening effort, and memory effort was evaluated. RESULTS: We analyzed pupil dilation both before each sentence (sentence baseline) as well as the dilation in response to each sentence relative to the sentence baseline (sentence dilation). The pupillometry data indicated a steeper increase of sentence baseline under recall compared to no recall, suggesting higher memory effort due to memory processing. This increase in sentence baseline was most prominent toward the end of the longer lists, that is, during the second half of six sentences. Without a recall task, sentence baseline declined over the course of the list. Noise reduction appeared to have a significant influence on effort allocation for listening, which was reflected in generally decreased sentence dilation. CONCLUSION: Our results showed that recording pupil dilation in a speech identification and recall task provides valuable insights beyond behavioral performance. It is a suitable tool to disentangle the allocation of effort to listening versus memorizing speech.

Sequential bilateral implantation in older children: Inter-implant map differences and their effects on functional outcomes.

OBJECTIVES: It is well established that sequential bilateral implantation offers functional benefits in speech in noise and sound localisation, although it can be challenging to get long-term unilateral users to adapt to the second implant. The aim of this study was to investigate programming differences between the two cochlear implants that can impact on performance outcomes. DESIGN: Cohort Study. PARTICIPANTS: Sixteen older children who received sequential implants in Ireland and with at least one-year experience with their sequential implant were included in this study. Children were categorised into two groups according to the time interval between the two implants: short if the time between the two implants was less than eight years and long if more than eight years. MAIN OUTCOME MEASURES: Dynamic ranges and current levels were compared for both implants. Functional outcome measures included sentence discrimination in quiet and in noise and sound localisation. RESULTS: Results show that for the children with long inter-implant delays, the dynamic range of their second implant was on average 34% less than the dynamic range of their first implant. This difference was driven by smaller comfort levels in the second implant compared to the first. Children with longer inter-implant delays also show lower speech discrimination scores with their second implant compared to children with shorter delays, in addition to no bilateral advantage in speech in noise, that is their performance in unilateral mode does not differ from the performance in bilateral mode. Finally, children with longer delays demonstrate poor performance in sound localisation compared to the children with shorter delays. CONCLUSION: Sequentially implanted older children show limited functional benefits from the second implant. The observed functional benefits are determined both by a short inter-implant delay and by having balanced dynamic ranges between the two implants.

Government roles in regulating medical tourism: evidence from Guatemala.

BACKGROUND: Regulation of the medical tourism and public health sectors overlap in many instances, raising questions of how patient safety, economic growth, and health equity can be protected. The case of Guatemala is used to explore how the regulatory challenges posed by medical tourism should be dealt with in countries seeking to grow this sector. METHODS: We conducted a qualitative case study of the medical tourism sector in Guatemala, through reviews and analyses of policy documents and media reports, key informant interviews (n = 50), and facility site-visits. RESULTS: Key informants were critical of the absence of effective public regulation of the emerging medical tourism sector, noting several regulatory gaps and the importance of filling them. These informants specifically expressed that: 1) The government should regulate medical tourism in Guatemala, thought there was disagreement as to which government sector should do so and how; 2) The government has not at this time regulated the medical tourism sector nor shown great interest in doing so; and 3) International accreditation could be used to augment domestic regulation. CONCLUSIONS: The intersection of domestic and international regulation of medical tourism has been largely unexplored. This case study advances new research in this area. It highlights the need for and dearth of regulatory protections in Guatemala and lessons for other, similarly situated countries. National regulatory models from Israel and Barbados could be adapted to the Guatemalan context. Global governance could help to protect national governments from any competitive disadvantages created by regulation. Underlying the concerns over growth in medical tourism, however, is how it contributes to the ongoing privatization of health care facilities worldwide. This trend risks undermining efforts to reach targets for Universal Health Coverage and exacerbating existing inequities in the global distribution of health and wealth.

Tele-Nephrology: A Feasible Way to Improve Access to Care for Patients with Kidney Disease Who Reside in Underserved Areas.

BACKGROUND: The Miami VA Healthcare System serves veterans in three South Florida counties: Miami-Dade, Broward, and Monroe, with an estimated veteran population of 175,000. To overcome geographical barriers and facilitate the access to nephrology clinics, we implemented provider-patient tele-nephrology using secured videoconferencing. METHODS: A retrospective and descriptive study design was used to evaluate the effect of the tele-nephrology clinic intervention. Multiple clinical indicators were included in the analysis: blood pressure (BP) control, stabilization of the renal function, and electrolyte/metabolic control. One hundred one patients who were evaluated in the clinic between 2013 and 2015 were included in the analysis, and the indicators were collected retrospectively. RESULTS: One hundred one patients were included in the analysis, with 95% of patients being male (n = 96) and 5% female (n = 5). The mean age was 65.5 years. Fifty patients had chronic kidney disease (CKD) stage III (49.5%), 14 patients had CKD stage IV (13%), and 8 patients had CKD stage II (7.9%). A one-way analysis of variance between subjects was conducted and showed that the effect of the tele-nephrology clinic intervention on reducing BP was statistically significant (systolic BP less than 140 p value <0.0001). Renal function stabilized but the creatinine changes over time were not statistically significant (p value: 0.50). Potassium showed a significant improvement in this sample (p value: 0.0076). Phosphorous and bicarbonate did not show a statistically significant improvement (p value 0.79 and 0.91, respectively). CONCLUSION: With the tele-nephrology clinic intervention, we were able to effectively improve BP and stabilize renal function in patients with kidney disease who reside in underserved areas.

Age-friendly initiatives: Mexico.

While the implementation of these initiatives varies globally and continues to face low uptake in the global south, it is crucial to underscore key ongoing efforts, particularly in developing nations. This allows us to have knowledge about progress and identify areas that require more effective strategies to advance the cause of global healthy aging. The aim of this mini-review was to describe some of the key age-friendly initiatives made in Mexico through Governmental and Non-Governmental entities to promote healthy aging, at different levels of health and social institutions, covering the healthcare systems, community, and education.

'The Mind' promotes brain synchronization: an ecological evaluation of brain synchronization in co-operative tasks.

This paper presents an ecologically valid approach for using EEG hyperscanning methods to assess levels of interbrain synchrony (IBS) in teams during co-operative tasks. We employ a card-based task in an out-of-the-lab setting to evaluate levels of neural synchrony between team members completing a co-operative task. We also examine the interplay between the recorded synchronization levels and the collective performance of the team.Clinical Relevance- This study provides a simplistic and ecologically valid setup with potential to bring a better understanding of brain synchronization in clinical settings where co-operation would improve outcomes, such as home care facilities and memory clinics.

Influence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8-12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Depth matters - Towards finding an objective neurophysiological measure of behavioral amplitude modulation detection based on neural threshold determination.

With increasing numbers undergoing intervention for hearing impairment at a young age, the clinical need for objective assessment tools of auditory discrimination abilities is growing. Amplitude modulation (AM) sensitivity has been known to be an important factor for speech recognition particularly among cochlear implant (CI) users. It therefore would be useful to develop objective measures of AM detection for future clinical assessment of CI users; this study aimed to verify the feasibility of a neurophysiological approach studying a cohort of normal-hearing participants. The mismatch waveform (MMW) was evaluated as a potential objective measure of AM detection for a low modulation rate (8 Hz). This study also explored the relationship between behavioral AM detection and speech-in-noise recognition. The following measures were obtained for 15 young adults with no known hearing impairment: (1) psychoacoustic sinusoidal AM detection ability for a modulation rate of 8 Hz; (2) neural AM detection thresholds estimated from morphology weighted cortical auditory evoked potentials elicited to various AM depths; and (3) AzBio sentence scores for speech-in-noise recognition. No significant correlations were found between speech recognition and behavioral AM detection measures. Individual neural thresholds were obtained from MMW data and showed significant positive correlations with behavioral AM detection thresholds. Neural thresholds estimated from morphology weighted MMWs provide a novel, objective approach for assessing low-rate AM detection. The findings of this study encourage the continued investigation of the MMW as a neural correlate of low-rate AM detection in larger normal-hearing cohorts and subsequently in clinical cohorts such as cochlear implant users.

Septic pleuritis and abdominal abscess formation caused by Rhodococcus equi in a foal.

A 3-month-old female Arabian horse was evaluated because of fever, respiratory distress, lethargy, and decreased appetite of 5 days' duration. Pleural effusion was diagnosed on the basis of ultrasonographic and radiographic examinations. Cytologic examination of pleural fluid collected via thoracocentesis revealed septic inflammation; bacteriologic culture of a sample of that fluid yielded Rhodococcus equi. A large intra-abdominal mass adjacent to the body wall was identified ultrasonographically. A specimen of the mass was collected via aspiration; the specimen was identified cytologically as purulent exudate that contained large numbers of rod-shaped bacteria, which confirmed abdominal abscess formation. Bacteriologic culture of a sample of the exudate also yielded R. equi. The foal was treated with azithromycin (10 mg/kg [4.5 mg/lb], PO, q 24 h for 5 days then q 48 h) and rifampin (5 mg/kg [2.3 mg/lb], PO, q 12 h) for 8 weeks and metronidazole (15 mg/kg [6.8 mg/lb], PO, q 8 h) for 3 weeks. Clinically, the foal responded to antimicrobial treatment within 2 weeks. At 8 weeks after the initial evaluation, ultrasonographic examination of the foal revealed resolution of the pleural effusion and abdominal abscess. In foals, R. equi infection typically results in pyogranulomatous pneumonia, and pleural effusion is an uncommon clinical sign. The combination of azithromycin and rifampin appears to be an effective treatment for R. equi infection in foals.

Cyclosporine and low-dose ketoconazole in renal transplant recipients: a single-center experience.

BACKGROUND: The high cost of cyclosporine A (CsA) is an impediment for low-income patients. Previous studies have used ketoconazole at doses between 200 and 400 mg/day to lower CsA consumption. METHODS: Ketoconazole and CsA were administered prospectively to renal transplant patients. Patients treated historically with CsA were used as a reference group. At different intervals posttransplant, clinical and laboratory data were recorded. RESULTS: The reference group (n=14) was treated with CsA from 1992 to 1997 and the CsA plus ketoconazole group (n=17) from 1998 to 2002. Follow-up was 76+/-22 and 29+/-14 months, respectively. CsA doses throughout the study were 4.0+/-1.3 and 1.6+/-0.6 mg/kg/day (a 60% reduction, P =0.00). Trough levels of CsA were 194+/-87 and 193+/-69 ng/mL, respectively. The ketoconazole dose was 54+/-17 mg/day. The monthly cost of CsA was reduced by 60%, including the cost of ketoconazole. CONCLUSIONS: CsA with ketoconazole resulted in a substantial dose and cost reduction that proved safe and effective.

Objective assessment of spectral ripple discrimination in cochlear implant listeners using cortical evoked responses to an oddball paradigm.

Cochlear implants (CIs) can partially restore functional hearing in deaf individuals. However, multiple factors affect CI listener's speech perception, resulting in large performance differences. Non-speech based tests, such as spectral ripple discrimination, measure acoustic processing capabilities that are highly correlated with speech perception. Currently spectral ripple discrimination is measured using standard psychoacoustic methods, which require attentive listening and active response that can be difficult or even impossible in special patient populations. Here, a completely objective cortical evoked potential based method is developed and validated to assess spectral ripple discrimination in CI listeners. In 19 CI listeners, using an oddball paradigm, cortical evoked potential responses to standard and inverted spectrally rippled stimuli were measured. In the same subjects, psychoacoustic spectral ripple discrimination thresholds were also measured. A neural discrimination threshold was determined by systematically increasing the number of ripples per octave and determining the point at which there was no longer a significant difference between the evoked potential response to the standard and inverted stimuli. A correlation was found between the neural and the psychoacoustic discrimination thresholds (R2=0.60, p<0.01). This method can objectively assess CI spectral resolution performance, providing a potential tool for the evaluation and follow-up of CI listeners who have difficulty performing psychoacoustic tests, such as pediatric or new users.

Cochlear implant artifact attenuation in late auditory evoked potentials: a single channel approach.

Recent evidence suggests that late auditory evoked potentials (LAEP) provide a useful objective metric of performance in cochlear implant (CI) subjects. However, the CI produces a large electrical artifact that contaminates LAEP recordings and confounds their interpretation. Independent component analysis (ICA) has been used in combination with multi-channel recordings to effectively remove the artifact. The applicability of the ICA approach is limited when only single channel data are needed or available, as is often the case in both clinical and research settings. Here we developed a single-channel, high sample rate (125 kHz), and high bandwidth (0-100 kHz) acquisition system to reduce the CI stimulation artifact. We identified two different artifacts in the recording: 1) a high frequency artifact reflecting the stimulation pulse rate, and 2) a direct current (DC, or pedestal) artifact that showed a non-linear time varying relationship to pulse amplitude. This relationship was well described by a bivariate polynomial. The high frequency artifact was completely attenuated by a 35 Hz low-pass filter for all subjects (n = 22). The DC artifact could be caused by an impedance mismatch. For 27% of subjects tested, no DC artifact was observed when electrode impedances were balanced to within 1 kΩ. For the remaining 73% of subjects, the pulse amplitude was used to estimate and then attenuate the DC artifact. Where measurements of pulse amplitude were not available (as with standard low sample rate systems), the DC artifact could be estimated from the stimulus envelope. The present artifact removal approach allows accurate measurement of LAEPs from CI subjects from single channel recordings, increasing their feasibility and utility as an accessible objective measure of CI function.

The endothelial nitric oxide synthase T-786c mutation, a treatable etiology of Prinzmetal's angina.

We assessed to what degree the endothelial nitric oxide synthase (eNOS) T-786C polymorphism, leading to reduced nitric oxide (NO) production-coronary artery spasm, was reversibly associated with Prinzmetal's variant angina (PVA). ENOS T-786C PCR analyses were done in 19 women, 8 men, 26 Caucasian, 1 African-American, median age 53, with well-documented PVA and in 72 healthy controls who did not differ by race or gender. Of the 27 cases, 7 (26%) were homozygous for wild-type normal eNOS (CC), 13 (48%) were T-786C heterozygotes (CT), and 7 (26%) were T-786C homozygotes (TT) vs controls, 44 (61%) CC, 27 (38%) TC, and 1 (1%) TT, P < 0.0001. The mutant eNOS T-786C allele frequency in PVA patients was 27/54 (50%) vs 29/144 (20%) in controls, P < 0.0001. On oral L-arginine (9.2 g/d) to increase production of NO for a median of 4.7 months in 16 PVA patients with symptomatic angina despite conventional nitrate-calcium channel blockers, using the Seattle Angina Questionnaire, satisfaction with symptom remission rose (median) from 50% to 100% (P = 0.004), satisfaction with angina frequency reduction rose from 65% to 80% (P = 0.02), satisfaction with treatment for symptoms rose from 38% to 88% (P = 0.001), and perception of overall life status rose from 25 to 71% (P = 0.0002). On L-arginine (median 4.7 months), in 20 patients, none had worsening of angina, and of 7 patients whose angina totally resolved, eNOS T-786C homozygosity was over-represented, P = 0 .04. The eNOS T-786C mutation appears to be a reversible etiology of PVA in patients whose angina may be ameliorated by L-arginine.

Auditory mismatch negativity in cochlear implant users: a window to spectral discrimination.

A cochlear implant (CI) can partially restore hearing in patients with severe to profound sensorineural hearing loss. However, the large outcome variability in CI users prompts the need for more objective measures of speech perception performance. Electrophysiological metrics of CI performance may be an important tool for audiologists in the assessment of hearing rehabilitation. Utilizing electroencephalography (EEG), it may be possible to evaluate speech perception correlates such as spectral discrimination. The mismatch negativity (MMN) of 10 CI subjects was recorded for stimuli containing different spectral densities. The neural spectral discrimination threshold, estimated by the MMN responses, showed a significant correlation with the behavioral spectral discrimination threshold measured in each subject. Results suggest that the MMN can be potentially used to obtain an objective estimate of spectral discrimination abilities in CI users.

Los Defectos Congénitos de la etapa I de la N-Glicosilación. Bases moleculares y manifestaciones clínicas / Congenital disorders due to deficiencies on the first step of the N-glycosylation pathway. Molecular basis and clinical manifestations

Los defectos congénitos de la glicosilación son un grupo de rápida expansión que presentan una amplia sintomatología y variado grado de severidad. La causa molecular se relaciona con la deficiencia en el proceso de N-glicosilación. Este proceso tiene lugar tanto en el retículo endoplasmático como en el aparato de Golgi y ocurre mediante dos etapas. Hasta la fecha, se han descrito más de 30 tipos de trastornos genéticos de la N glicosilación. CDG-Ia es el más frecuente de todos. Los principales hallazgos clínicos resultan: el retraso psicomotor, ataxia, convulsiones, retinopatía, fibrosis hepática, coagulopatías, fallo de medro, rasgos dismórficos que incluyen las pezones invertidos y la distribución anómala de grasa subcutánea. Solo existe tratamiento efectivo demostrado para el CDG-Ib. Se realiza una actualización de los CDG que involucran afectación de la primera etapa de este proceso…(AU)

Biografía del eminente cardiólogo cubano Dr Néstor Reynaldo Calafell Vázquez / Biography of the eminent cardiologist Nestor Reynaldo Calafell Vázquez MD

El 29 de octubre del 2009, justo a las 2:50 p.m dejó de latir el corazón del Dr. Néstor Reynaldo Calafell Vázquez, eminente cardiólogo cubano, que había nacido el 26 de Mayo de 1927, en el seno de un humilde hogar de Manzanillo, actual provincia Granma, hijo de un padre albañil y una madre ama de casa. Inició sus primeros estudios en la educación primaria en escuelas particulares de su ciudad natal, continuando en cuarto grado en la escuela pública Bazán. En el año 1942 ingresó por examen en el Instituto de Segunda Enseñanza de Manzanillo y en el año 1947 ingresó en la Universidad de La Habana para estudiar Medicina, obtuvo las matrículas gratis durante toda la carrera por su excelente expediente académico y se graduó de médico en 1954...