Electrocochleographic frequency-following responses as a potential marker of age-related cochlear neural degeneration.

Auditory nerve (AN) fibers that innervate inner hair cells in the cochlea degenerate with advancing age. It has been proposed that age-related reductions in brainstem frequency-following responses (FFR) to the carrier of low-frequency, high-intensity pure tones may partially reflect this neural loss in the cochlea (Märcher-Rørsted et al., 2022). If the loss of AN fibers is the primary factor contributing to age-related changes in the brainstem FFR, then the FFR could serve as an indicator of cochlear neural degeneration. In this study, we employed electrocochleography (ECochG) to investigate the effects of age on frequency-following neurophonic potentials, i.e., neural responses phase-locked to the carrier frequency of the tone stimulus. We compared these findings to the brainstem-generated FFRs obtained simultaneously using the same stimulation. We conducted recordings in young and older individuals with normal hearing. Responses to pure tones (250 ms, 516 and 1086 Hz, 85 dB SPL) and clicks were recorded using both ECochG at the tympanic membrane and traditional scalp electroencephalographic (EEG) recordings of the FFR. Distortion product otoacoustic emissions (DPOAE) were also collected. In the ECochG recordings, sustained AN neurophonic (ANN) responses to tonal stimulation, as well as the click-evoked compound action potential (CAP) of the AN, were significantly reduced in the older listeners compared to young controls, despite normal audiometric thresholds. In the EEG recordings, brainstem FFRs to the same tone stimulation were also diminished in the older participants. Unlike the reduced AN CAP response, the transient-evoked wave-V remained unaffected. These findings could indicate that a decreased number of AN fibers contributes to the response in the older participants. The results suggest that the scalp-recorded FFR, as opposed to the clinical standard wave-V of the auditory brainstem response, may serve as a more reliable indicator of age-related cochlear neural degeneration.

Predicting early auditory evoked potentials using a computational model of auditory-nerve processing.

Non-invasive electrophysiological measures, such as auditory evoked potentials (AEPs), play a crucial role in diagnosing auditory pathology. However, the relationship between AEP morphology and cochlear degeneration remains complex and not well understood. Dau [J. Acoust. Soc. Am. 113, 936-950 (2003)] proposed a computational framework for modeling AEPs that utilized a nonlinear auditory-nerve (AN) model followed by a linear unitary response function. While the model captured some important features of the measured AEPs, it also exhibited several discrepancies in response patterns compared to the actual measurements. In this study, an enhanced AEP modeling framework is presented, incorporating an improved AN model, and the conclusions from the original study were reevaluated. Simulation results with transient and sustained stimuli demonstrated accurate auditory brainstem responses (ABRs) and frequency-following responses (FFRs) as a function of stimulation level, although wave-V latencies remained too short, similar to the original study. When compared to physiological responses in animals, the revised model framework showed a more accurate balance between the contributions of auditory-nerve fibers (ANFs) at on- and off-frequency regions to the predicted FFRs. These findings emphasize the importance of cochlear processing in brainstem potentials. This framework may provide a valuable tool for assessing human AN models and simulating AEPs for various subtypes of peripheral pathologies, offering opportunities for research and clinical applications.

Streptococcus pyogenes infections in Spanish children before and after the COVID pandemic. Coming back to the previous incidence.

INTRODUCTION: Group A Streptococcus (GAS) causes mild diseases, and unfrequently invasive infections (iGAS). Following the December 2022 alert from the United Kingdom regarding the unusual increase in GAS and iGAS infections, we analyzed the incidence of GAS infections in 2018-2022 in our hospital. METHODS: We conducted a retrospective study of patients seen in a pediatric emergency department (ED) diagnosed with streptococcal pharyngitis and scarlet fever and patients admitted for iGAS during last 5 years. RESULTS: The incidence of GAS infections was 6.43 and 12.38/1000 ED visits in 2018 and 2019, respectively. During the COVID-19 pandemic the figures were 5.33 and 2.14/1000 ED visits in 2020 and 2021, respectively, and increased to 10.2/1000 ED visits in 2022. The differences observed were not statistically significant (p=0.352). CONCLUSIONS: In our series, as in other countries, GAS infections decreased during the COVID-19 pandemic, and mild and severe cases increased considerably in 2022, but did not reach similar levels to those detected in other countries.

Emergency department evaluation of transplanted children with COVID-19.

BACKGROUND: Children usually have an asymptomatic or mild course of SARS-CoV-2 infection, studies in immunocompromised patients have shown a different evolution. The aim of this study was to describe the clinical, laboratory, and radiologic manifestations of pediatric solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients testing positive for SARS-CoV-2. METHODS: A multicenter retrospective, observational descriptive study was conducted in 3 tertiary hospitals in Madrid (Spain) between March 2020 and December 2022. Consecutive patients aged 0-18 attending the corresponding pediatric emergency departments with a positive result in the real-time polymerase chain reaction test or antigenic test to detect SARS-CoV-2 in the nasopharyngeal sample were included. RESULTS: A total of 31 children were included in the study. Sixteen (51.6%) were patients with HSCT and 15 (48.3) were patients with SOT. The median time from transplantation to COVID-19 was 1.2 years (IQR:0.5-5.1). The SOT cohort included liver (n = 4, 12.9%), kidney (n = 4, 12.9%), heart (n = 3, 9.7%), multivisceral (n = 3, 9.7%), and lung (n = 1, 3.2%). Of the 31 patients, only one was asymptomatic. The most common symptom on presentation was fever (76.7%). Abnormalities were seen on chest X-ray in 8 (66.6%) of the 12 patients. There was no significant difference in clinical manifestations, lymphopenia and radiological findings regardless of the type of transplantation or immunosuppression status. Thirteen patients (41.9%) were hospitalized. There were no patient deaths. CONCLUSIONS: In our study, we found that the clinical course and outcome of SOT and HSCT pediatric patients with COVID-19 were generally favorable.

Trends in Sexual Health of Gay, Bisexual, and Other Men Who Have Sex with Men, and Transgender Individuals: Apps Driven Testing Program for HIV and Other STIs in Barcelona, Spain (2016-2023).

Gay, bisexual and other men who have sex with men (GBMSM) and transgender individuals face heightened risks of HIV and other sexually transmitted infections (STIs). Surveillance within these populations is critical, and community testing services play a pivotal role in preventing and controlling HIV and STIs. This study investigates the trends in HIV, syphilis and hepatitis C (HCV) infections among participants in an apps-driven rapid test program from 2016 to 2023 in Barcelona, Spain, examining associated factors. Trend analysis utilized Wilcoxon-type test and associated factors were determined through multivariate logistic analysis. The prevalence of new HIV diagnosis was 1.81% (CI 1.18-2.64), active syphilis was 3.37% (CI 2.46-4.50) and acute HCV was 0.40% (CI 0.11-1.02). While infection rates showed no significant changes, there was significant increasing in sex work and chemsex and decreasing in condom use. Additionally, a peak in dating apps use for sex and a specific reduction in number of sexual partners were observed in 2020. Factors associated with HIV diagnoses included migrant status (aOR = 11.19; CI 2.58-48.53) and inconsistent condom use during the previous 12 months (aOR = 3.12; CI 1.02-9.51). For syphilis, associated factors were migrant status (aOR = 2.46; CI 1.14-5.29), inconsistent condom use (aOR = 3.38; CI 1.37-8.36), and chemsex practice during the previous 12 months (aOR = 2.80; CI 1.24-6.30). Our findings emphasize the need for tailored interventions, including culturally sensitive outreach for migrants and comprehensive strategies addressing substance use in sexual contexts. Technological innovations and targeted educational initiatives could reduce the burden of HIV and STIs within the GBMSM and transgender communities, providing valuable insights for public health strategies.

[Influencia de la pandemia de la COVID-19 en la distribución de la bronquiolitis aguda en España.] / Influencia de la pandemia de la COVID-19 en la distribución de la bronquiolitis aguda en España.

OBJECTIVE: Bronchiolitis is the leading cause of hospitalization in children under one year of age, with annual epidemics. Since the onset of the SARS-CoV-2 coronavirus disease pandemic (COVID-19), there has been a change in the transmission of other respiratory viruses. Our aim in this paper was to describe how COVID-19 had affected the distribution of acute bronchiolitis in our country. METHODS: We conducted a retrospective descriptive study of the cases of bronchiolitis treated in a sample of Spanish hospitals belonging to four autonomous communities. A chi-square test and Student's t- test were used to compare epidemiological and demographic variables between patients attending the hospital with bronchiolitis during January 2021-June 2021 with patients attending the hospital in the previous three years (2018-2020). RESULTS: We analyzed 6,124 cases of bronchiolitis (58.8% males and 41.2% females). The mean age was 0.5 years (SD: 0.4). In 2020, we observed a decrease of bronchiolitis cases compared to 2019 of 67%. During 2020 and 2021, the epidemic season started in January-February and peaked in June. During the first half of 2021, the highest percentage of admissions for bronchiolitis associated with RSV infection was observed in hospitals in central Spain corresponding to the Autonomous Community of Madrid (78.5% of admissions). CONCLUSIONS: The COVID-19 pandemic significantly modifies the seasonality of bronchiolitis. In our country, the flow and distribution of the disease are not uniform. It starts in the center of Spain and ends on the coast.

OBJETIVO: La bronquiolitis es la primera causa de hospitalización en menores de un año, presentándose en forma de epidemias anuales. Desde el inicio de la pandemia por la enfermedad causada por el coronavirus SARS-CoV-2 (COVID-19) se ha producido un cambio en la transmisión de otros virus respiratorios. Nuestro objetivo en este trabajo fue describir cómo había afectado la pandemia de la COVID-19 a la distribución de la bronquiolitis aguda en nuestro país. METODOS: Realizamos un estudio descriptivo retrospectivo de los casos de bronquiolitis atendidos en una muestra de hospitales españoles que pertenecían a cuatro comunidades autónomas. Empleado el test chi-cuadrado y la prueba t de Student comparamos variables epidemiológicas y demográficas de los casos de bronquiolitis atendidos durante enero de 2021 y junio 2021, con los tres años anteriores (2018-2020). RESULTADOS: Analizamos 6.124 casos de bronquiolitis (58,8% varones y 41,2% mujeres). La media de edad fue de 0,5 años (DE: 0,4). En 2020 observamos un descenso de casos de bronquiolitis con respecto a 2019 del 67%. Durante 2020 y 2021 la temporada epidémica empezó en enero-febrero y alcanzó su pico máximo en junio. Durante el primer semestre de 2021, el porcentaje más elevado de ingresos por bronquiolitis asociados a infección VRS fue observado en hospitales del centro de España correspondientes a la Comunidad Autónoma de Madrid (78,5% de los ingresos). CONCLUSIONES: La pandemia por la COVID-19 modifica de manera significativa la estacionalidad de la bronquiolitis. En nuestro país, el flujo y distribución de la enfermedad no es uniforme, comenzado por el centro peninsular y, por último, la zona litoral.

Influencia de la pandemia dela COVID-19 en la distribución de la bronquiolitis aguda en España / Influence of the pandemic of COVID-19 in distribution of acute bronchiolitis in Spain

Fundamentos: La bronquiolitis es la primera causa de hospitalización en menores de un año, presentándose en forma de epidemias anuales. Desde el inicio de la pandemia por la enfermedad causada por el coronavirus SARS-CoV-2 (COVID-19) se ha producido un cambio en la transmisión de otros virus respiratorios. Nuestro objetivo en este trabajo fue describir cómo había afectado la pandemia de la COVID-19 a la distribución de la bronquiolitis aguda en nuestro país. Métodos: Realizamos un estudio descriptivo retrospectivo de los casos de bronquiolitis atendidos en una muestra de hospitales españoles que pertenecían a cuatro comunidades autónomas. Empleado el test chi-cuadrado y la pruebat de Student comparamos variables epidemiológicas y demográficas de los casos de bronquiolitis atendidos durante enero de 2021 y junio 2021, con los tres años anteriores (2018-2020). Resultados: Analizamos 6.124 casos de bronquiolitis (58,8% varones y 41,2% mujeres). La media de edad fue de 0,5 años (DE: 0,4). En 2020 observamos un descenso de casos de bronquiolitis con respecto a 2019 del 67%. Durante 2020 y 2021 la temporada epidémica empezó en enero-febrero y alcanzó su pico máximo en junio. Durante el primer semestre de 2021, el porcentaje más elevado de ingresos por bronquiolitis asociados a infección VRS fue observado en hospitales del centro de España correspondientes a la Comunidad Autónoma de Madrid (78,5% de los ingresos). Conclusiones: La pandemia por la COVID-19 modifica de manera significativa la estacionalidad de la bronquiolitis. En nuestro país, el flujo y distribución de la enfermedad no es uniforme, comenzado por el centro peninsular y, por último, la zona litoral.(AU)

Background: Bronchiolitis is the leading cause of hospitalization in children under one year of age, with annual epidemics. Sincethe onset of the SARS-CoV-2 coronavirus disease pandemic (COVID-19), there has been a change in the transmission of other respiratory viruses. Our aim in this paper was to describe how COVID-19 had affected the distribution of acute bronchiolitis in our country. Methods: We conducted a retrospective descriptive study of the cases of bronchiolitis treated in a sample of Spanish hospitals belonging to four autonomous communities. A chi-square test and Student’s t- test were used to compare epidemiological and demographicvariables between patients attending the hospital with bronchiolitis during January 2021-June 2021 with patients attending the hospital in the previous three years (2018-2020). Results: We analyzed 6,124 cases of bronchiolitis (58.8% males and 41.2% females). The mean age was 0.5 years (SD: 0.4). In 2020, weobserved a decrease of bronchiolitis cases compared to 2019 of 67%. During 2020 and 2021, the epidemic season started in January-February and peaked in June. During the first half of 2021, the highest percentage of admissions for bronchiolitis associated with RSVinfection was observed in hospitals in central Spain corresponding to the Autonomous Community of Madrid (78.5% of admissions).Conclusions: The COVID-19 pandemic significantly modifies the seasonality of bronchiolitis. In our country, the flow and distri-bution of the disease are not uniform. It starts in the center of Spain and ends on the coast.(AU)

Volatile Organic Compounds from Cassava Plants Confer Resistance to the Whitefly Aleurothrixus aepim (Goeldi, 1886).

Cassava is an essential tuber crop used to produce food, feed, and beverages. Whitefly pests, including Aleurothrixus aepim (Goeldi, 1886) (Hemiptera: Aleyrodidae), significantly affect cassava-based agroecosystems. Plant odours have been described as potential pest management tools, and the cassava clone M Ecuador 72 has been used by breeders as an essential source of resistance. In this study, we analysed and compared the volatile compounds released by this resistant clone and a susceptible genotype, BRS Jari. Constitutive odours were collected from young plants and analysed using gas chromatography-mass spectrometry combined with chemometric tools. The resistant genotype released numerous compounds with previously described biological activity and substantial amounts of the monoterpene (E)-ß-ocimene. Whiteflies showed non-preferential behaviour when exposed to volatiles from the resistant genotype but not the susceptible genotype. Furthermore, pure ocimene caused non-preferential behaviour in whiteflies, indicating a role for this compound in repellence. This report provides an example of the intraspecific variation in odour emissions from cassava plants alongside information on odorants that repel whiteflies; these data can be used to devise whitefly management strategies. A better understanding of the genetic variability in cassava odour constituents and emissions under field conditions may accelerate the development of more resistant cassava varieties.

Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy.

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3-12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty® (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4+ T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty®-vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations.

Response Rate, Acceptability and Effectiveness of an Intervention Offering HIV/STI Testing Via Apps Among Gay, Bisexual, and Other Men Who Have Sex With Men in Barcelona, Spain, from 2016 to 2020.

We evaluated the response rate, acceptability, and effectiveness of a preventive programme offering rapid HIV and other STI testing, as well as sexual counselling to gay, bisexual, and other men who have sex with men (GBMSM) via dating apps over a 4-year period. The programme was carried out in 9 out of the 10 districts in the city of Barcelona, Spain. The response rate was defined as the proportion of people responding to the message sent, acceptability as the proportion of those responding favourably, and effectiveness as the proportion of users requesting a test. We performed univariate analysis and multivariate logistic regression in relation with the response rate, acceptability and effectiveness. A total of 5,254 messages were send to different users. The response rate was 33.1% (n = 1,741), acceptability was 86.2% (n = 1,500), and effectiveness was 10.1% (n = 532). The factors associated with user response were recent connection to the app (aOR = 1.85; CI:1.39-2.46) and the presence of a profile photograph (aOR = 1.34; CI:1.11-1.64). Acceptability was associated with recent connection to the app (aOR = 1.98; CI:1.09-3.58). Effectiveness was associated with lower reported age (aOR = 0.98; CI:0.97-0.99), contact before 14:00 (aOR = 2.47; CI: 1.77-3.46), and recent connection to the app (aOR = 4.89; CI:1.98-12.08). Effectiveness was also greater in districts that were more disadvantaged or had fewer sexual health services. This study demonstrates that the use of these apps is an acceptable and effective method of prevention and sexual health promotion in GBMSM in this setting and identifies the associated factors that could guide such interventions.

Neurofibromatosis tipo 1 o enfermedad de Von Recklinghausen. Presentación de caso

La neurofibromatosis tipo I o enfermedad de Von Recklinghausen es una de las enfermedades genéticas que afectan el sistema nervioso, denominada así por su origen común embrionario. Es una enfermedad autosómica dominante, progresiva, de evolución impredecible, que afecta la piel y el sistema nervioso central y periférico. Se presenta el caso de una escolar, femenina, de siete años de edad que ingresó en el Hospital Pediátrico Paquito Gonzáles Cueto debido a la presencia de varias manchas en la piel color "café con leche". Se recogió como antecedente familiar la presencia de neurofibromatosis tipo 1 en la abuela y bisabuela materna, esta última ya fallecida por dicha causa. Al examen físico se constataron nódulos de Lisch en espesor del iris del ojo izquierdo. Los estudios de imágenes evidenciaron varias lesiones nodulares hiperintensas en T2 y FLAIR, a nivel de la cápsula interna y externa bilateral y ventricular izquierda, la mayor de 20 x 11 mm, así como imagen hipointensa a nivel del nervio óptico izquierdo, de 7 mm. Se diagnosticó como neurofibromatosis tipo I. Por ser una de las enfermedades menos estudiadas en nuestro medio se decidió la publicación de este caso.

Neurofibromatosis type I or Von Recklinghausen's disease is one of the genetic diseases that affect the nervous system, named for its common embryonic origin. It is an autosomal dominant, progressive disease with an unpredictable course that affects the skin and the central and peripheral nervous system. The case of a seven-year-old female schoolchild who was admitted to the Paquito Gonzáles Cueto Pediatric Hospital due to the presence of several "coffee-with-milk" spots on her skin is presented. The presence of type 1 neurofibromatosis in her maternal grandmother and great-grandmother, the latter already deceased from said cause, was collected as a family history. On physical examination, Lisch nodules were found in the thickness of the iris of the left eye. Imaging studies revealed several hyperintense nodular lesions on T2 and FLAIR, at the level of the internal and external bilateral and left ventricular capsule, the largest measuring 20 x 11 mm, as well as a hypointense image at the level of the left optic nerve, measuring 7 mm. It was diagnosed as neurofibromatosis type I. Because it is one of the least studied diseases in our environment, it was decided to publish this case.

Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study.

In the current post-pandemic era, recipients of an allogeneic hematopoietic stem cell transplant (HCT) deserve special attention. In these vulnerable patients, vaccine effectiveness is reduced by post-transplant immune-suppressive therapy; consequently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is often associated with elevated morbidity and mortality. Characterizing SARS-CoV-2 adaptive immunity transfer from immune donors to HCT recipients in the context of immunosuppression will help identify optimal timing and vaccination strategies that can provide adequate protection to HCT recipients against infection with evolving SARS-CoV-2 variants. We performed a prospective observational study (NCT04666025 at ClinicalTrials.gov) to longitudinally monitor the transfer of SARS-CoV-2-specific antiviral immunity from HCT donors, who were either vaccinated or had a history of COVID-19, to their recipients via T-cell replete graft. Levels, function, and quality of SARS-CoV-2-specific immune responses were longitudinally analyzed up to 6 months post-HCT in 14 matched unrelated donor/recipients and four haploidentical donor/recipient pairs. A markedly skewed donor-derived SARS-CoV-2 CD4 T-cell response was measurable in 15 (83%) recipients. It showed a polarized Th1 functional profile, with the prevalence of central memory phenotype subsets. SARS-CoV-2-specific IFN-γ was detectable throughout the observation period, including early post-transplant (day +30). Functionally experienced SARS-CoV-2 Th1-type T cells promptly expanded in two recipients at the time of post-HCT vaccination and in two others who were infected and survived post-transplant COVID-19 infection. Our data suggest that donor-derived SARS-CoV-2 T-cell responses are functional in immunosuppressed recipients and may play a critical role in post-HCT vaccine response and protection from the fatal disease. Clinical trial registration: clinicaltrials.gov, identifier NCT04666025.