P = 0.044], RMR per BMI , and RMR per FFM  using the NOVA score was observed after adjusting for confounders. This association disappeared after inclusion of each inflammatory marker. All the markers may inversely mediate the relationship between the mentioned variables and the NOVA score. hs-CRP and MCP-1 also had a negative effect on the relationship between the NOVA score and RMR deviation. Finally, UPF intake is likely related with the RMR, mediated through changes in the production of hs-CRP, PAI-1, MCP-1, and IL-1β.The resting metabolic rate (RMR) represents the largest component of total daily energy expenditure. The sale of ultra-processed foods (UPF) is increasing globally; however, UPF can have many adverse effects, including increasing inflammatory markers and altering RMRs. This cross-sectional study included 285 healthy overweight and obese women. Anthropometric measurements were evaluated using a bioelectrical impedance analyzer InBody 770 scanner. High-sensitivity C-reactive protein (hs-CRP), plasminogen activator-1 (PAI-1), monocyte chemoattractant protein (MCP-1), and interleukin-1 beta (IL-1β) blood levels were measured after a 12-h fasting. Indirect calorimetry was used to evaluate the RMR by using the Weir equation, and RMR deviation , RMR per body mass index (BMI), and free fat mass (FFM) were estimated. A validated food frequency questionnaire (FFQ) was used, and seven groups of UPFs were extracted based on the NOVA method. A negative association between the RMR [β = −0.159, 95% confidence interval (CI): −0.471, −0.052,  Knowledge of the resting metabolic rate (RMR) is necessary because it represents the largest component of total daily energy expenditure and has ramifications for nutrition support. Obesity and alterations in the RMR have a close link ; indeed,There are serious concerns about ultra-processed food (UPF) intake and obesity . The salTo the best of our knowledge, no study has evaluated the impact of inflammatory markers on the relationship between RMR and UPF intake, using the NOVA classification, in Iran. Therefore, this study was designed to assess the possible mediatory role of inflammatory markers in the association between ultra-processed foods and the resting metabolic rate.2 for overweight and 30 kg/m2 for obesity, and without any chronic diseases, like hypertension, kidney or liver disorders, and cardiovascular diseases, which was ascertained by a face-to-face anamnesis interview. Women who were smokers; were alcohol consumers; had prescribed medication; and were pregnant, breastfeeding, or in menopausal stage; or had a history of weight loss in the last 6 months were excluded. In addition, only participants with a total energy intake between 800 and 4,200 kcal/d were included  scores 25–29.9 kg/mincluded .This study was conducted according to the guidelines of the Declaration of Helsinki, and all procedures involving human subjects/patients were approved by the ethics committee of Tehran University of Medical Sciences (TUMS) with the following identification: IR.TUMS.VCR.REC.1398.463. Written informed consent was obtained from all patients prior to participation.r = 0.98. BFM (kg), free fat mass (FFM) (kg), and fat mass index (FMI) (kg/m2) were extracted. The height of the participants was measured with a Seca 216 stadiometer, to the nearest 0.1 cm, with the participants in a standing position and unshod. The arm muscle circumference (cm) of the participants were also measured according to standard kinanthropometrist guidelines.Weight, BMI, and body fat mass (BFM) were measured using a multi-frequency bioelectrical impedance analyzer (BIA) InBody 770 scanner , where the women wore light clothes, without any metal subjects, and in accordance with manufacturer’s protocols. Anthropometric measurements were conducted between 8 and 9 a.m., after 12 h of fasting. The participants were asked to refrain from any non-habitual physical activity for the preceding 72 h. The test–re-test reliability of BIA in our laboratory was After fasting for 12 h, blood samples were drawn from the participants. The samples of blood were collected in parent tubes containing 0.1 EDTA, and tests were analyzed utilizing the Auto-Analyzer BT 1500 . hs-CRP, PAI-1, MCP-1, and interleukin-1 beta (IL-1β) levels were measured by an immunoturbidimetric test using the Pars Azmoon kit . Serum levels of high-density lipoprotein cholesterol (HDL-C), fasting blood sugar (FBS), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), insulin, and triglyceride (TG) were also measured. Insulin resistance was assessed as HOMA-IR (homeostasis model assessment-estimated insulin resistance) = [glucose] (mmol/l) × [insulin] (μU/ml)/22.5 .2 consumed (liter) × 3.941 + produced Co2 (liter) × 1.11] × 1,440 min/d by assessing the amount of CO2 produced and O2 consumed through a one-way valve between the participants and the machine  is considered an accurate method of determining the RMR and was used to evaluate the RMR after an overnight fast. Respiratory gases were gathered using the MetaLyzer 3B-R3  spirometer. The participants were asked to refrain from the consumption of caffeine and vigorous activity for a day prior to RMR measurements. The participants were asked to sleep in a silent place in a temperature between 24 and 26°C the night before the test and be free from emotional stress. Gaseous exchange was analyzed in the last 20 min of the resting time and during a minimum of 5 consecutive minutes in a steady-state condition. The RMR was measured using the Weir equation: RMR = [O machine . RMR dev machine –29.A validated food frequency questionnaire (FFQ), with 147 items, was used to assess the average food consumption of the participants over the past year . All dievia the short form of the International Physical Activity Questionnaire (IPAQ)  of the participants was also evaluated e (IPAQ) . The metpost hoc tests were used to investigate differences between tertiles. Linear regression was also used to investigate the relationship between outcomes and exposure in crude and two adjusted models and the role of inflammatory markers. Model 1 was adjusted for age, energy intake, BMI, physical activity, job status, and supplement intake. In model 2, additional controlling for legumes and vegetables was conducted. The results are shown as a beta (β) with 95% confidence intervals (95% CI). Pearson correlation was utilized to discern the association between inflammatory markers, RMR, and NOVA score. All analyses were conducted using Statistical Package for Social Sciences) SPSS) version 25 software , where P < 0.05 was considered statistically significant.The normality of data was evaluated using a Kolmogorov–Smirnov test. General characteristics of the participants within different tertiles of the NOVA score were described as mean ± standard deviation (SD) for quantitative variables and frequency (%) for categorical variables. Chi-square tests and one-way analysis of variance (ANOVA) and analysis of covariance (ANCOVA) were used for categorical variables and dietary intake in order to compare the differences among tertiles of NOVA scores. The NOVA score was divided into three groups . Bonferroni via non-dairy beverages (39.12), and the smallest contribution was from oils and sauces (4.33%). General characteristics of the participants across NOVA score tertiles are shown in 2, respectively. In addition, the total mean (SD) of serum levels of hs-CRP, IL-1β, MCP-1, and PAI-1 was 4.31 (4.65), 2.73 (0.94), 50.69 (92.46), and 16.10 (29.92) mg/dl, respectively. A total of 142 women had a moderate income, and 148 were taking dietary supplements. Age and height were significantly different among NOVA tertiles (P < 0.05) in the crude model. After adjusting for confounding variables, such as age, BMI, PA, and energy intake, hs-CRP, and age were all significant (P < 0.05) (As shown in  < 0.05) .P < 0.05). After adjusting for energy, vegetables (P = 0.003), legumes (P = 0.04), linolenic acid (P = 0.02), total fiber (P < 0.001), beta-carotene (P = 0.01), vitamin B1 (P = 0.002), B6 (P < 0.001), B9 (P < 0.001), biotin (P = 0.01), magnesium (P = 0.002), copper (P = 0.008), and chromium (P = 0.009) remained significantly different.The dietary intake of subjects between NOVA tertiles is shown in P = 0.04).According to P = 0.038) with the NOVA score was observed. This negative relationship remained after adjusting for all confounders in model 2. In addition, a negative association was appeared between the NOVA score and RMR , and the RMR per FFM  in model 2.The relationship between the RMR and NOVA score is shown in r = 0.146, P = 0.024) and RMR per FFM , respectively.The correlation between inflammatory markers and the RMR variables is shown in P-value primary = 0.04), RMR per BMI , and RMR per FFM  is shown in P-value after = 0.54), IL-1β , MCP-1, and PAI-1 as confounding variables, along with the other confounders in model 2, a potential negative relationship between the NOVA score and RMR per BSA was evident. In addition, hs-CRP (P = 0.564) and MCP-1 (P = 0.911) also had a possible negative mediatory role in the relationship between NOVA score groups and RMR deviation from normal.The mediatory role of inflammatory markers on the relationship between UPF intakes and RMR is shown in To the author’s knowledge, this is the first study to have investigated the possible mediatory role of inflammatory markers on the relationship between UPF and RMR in obese and overweight women. In this study, we found that with increasing NOVA scores, RMR deviation from the calculated normal RMR was increased, which indicates that with increasing UPF consumption, RMR decreased. In addition, a significant negative association between the RMR, RMR per BMI, and RMR per FFM, with NOVA score was observed after adjusting all confounders. This suggests that all the included markers may inversely mediate the relationship between the mentioned variables and NOVA score. In addition, hs-CRP and MCP-1 also had a possible negative mediatory role in the relationship between NOVA score groups and RMR deviation from normal.High levels of CRP indicate low-grade inflammation that is, often, associated with several non-communicable diseases, including obesity, cardiovascular disease (CVD), and diabetes –37. In aIn a group of healthy individuals with normal weight and overweight, the association between RMR and hs-CRP levels, indicative of inflammation, was investigated, and the authors reported that sex significantly affects the age-related changes in body composition, in addition to changes in body composition–REE relationship . From a The study by Bibiloni et al. showed an association between omega-3 and PIA-1 PUFAs in healthy women . PUFA inIn a randomized controlled trial performed by Hall et al., it was reported that energy intake was higher during adherence to a UPF diet . ParticiEvidence is emerging regarding the mechanisms that strengthen the link between UPFs and adverse health outcomes. The mechanisms proposed are as follows: poor nutritional profile, UPFs are rich in sodium, added sugars, trans fats, and replace unprocessed foods in the diet –70, decrCarbohydrate metabolism is more energy-intensive than fat metabolism, while protein metabolism requires the most energy –81. ProcThe strengths of this study are the use of an FFQ questionnaire, which has been specifically validated in the Iranian population. Nevertheless, residual confounding related to recall bias must be acknowledged. Examining this association in one gender and only in Tehran represent limitations of this study because these results cannot be extrapolated to the entire Iranian population and all individuals. The cross-sectional design of this study precludes causal inferences being made. In addition, using BIA may overestimate lean body mass.Ultra-processed foods may be related with changes in the production and secretion of cytokines and inflammatory factors and, ultimately, cause inflammation and reduced RMRs. A negative association between the RMR, RMR per BMI, and RMR per FFM with the NOVA score was observed in the present study. UPF intake is likely related with the RMR, RMR per BMI, and RMR per FFM, mediated by the production of hs-CRP, PAI-1, MCP-1, and IL-1β. hs-CRP and MCP-1 levels also had a possible negative mediatory role in the relationship between NOVA score groups and RMR deviation from normal. Given the novel evidence provided, further work, in the form of interventional studies, is needed in this area.The original contributions presented in this study are included in the article/The studies involving human participants were reviewed and approved by the Tehran University of Medical Sciences and Health Services. The patients/participants provided their written informed consent to participate in this study.NB and FS designed the project. FS collected the samples and analyzed the data. NB and SN wrote the manuscript. FS, CC, and NB reviewed and edited the manuscript. KM conducted the research and had primary responsibility for the final content. All authors read and approved the final manuscript.


In this analysis, 10,687 additional sequences from samples from HIV-1-infected individuals collected in Spain in 1999–2019 were also included to assign TC membership and to determine TCs’ sizes. TCs were defined as those which included viruses from ≥4 individuals, at least 50% of them Spaniards, and with ≥0.95 Shimodaira-Hasegawa-like node support in the phylogenetic tree. Factors associated to TCs were evaluated using odds ratios (OR) and their 95% CI. Fifty-one percent of NDs grouped in 162 TCs. Male patients  and men having sex with men  had higher odds of belonging to a TC compared to female and heterosexual patients, respectively. Individuals from Latin America , North Africa , and especially Sub-Saharan Africa  were inversely associated to belonging to TCs compared to native Spaniards. Our results show that TCs are important components of the HIV-1 epidemics in the two Spanish regions studied, where transmission between MSM is predominant. The majority of migrants were infected with viruses not belonging to TCs that expand in Spain. Molecular epidemiology is essential to identify local peculiarities of HIV-1 propagation. The early detection of TCs and prevention of their expansion, implementing effective control measures, could reduce HIV-1 infections.Viruses of HIV-1-infected individuals whose transmission is related group phylogenetically in transmission clusters (TCs). The study of the phylogenetic relations of these viruses and the factors associated with these individuals is essential to analyze the HIV-1 epidemic. In this study, we examine the role of TCs in the epidemiology of HIV-1 infection in Galicia and the Basque County, two regions of northern Spain. A total of 1,158 HIV-1-infected patients from both regions with new diagnoses (NDs) in 2013–2018 were included in the study. Partial HIV-1  The HIV-1 epidemic is still one of the major public health problems in Spain. Around 3,500–4,000 new diagnoses (NDs) of HIV-1 infection are reported every year, with an estimated incidence of NDs of 7.5 per 100,000 population in 2019 . A decreMolecular epidemiology is an important tool for describing the HIV-1 epidemic . IndividNational databases of protease and reverse transcriptase (Pr-RT) sequences, primarily obtained for antiretroviral drug resistance testing, contain valuable data about HIV-1 expansion and have been used in molecular epidemiology studies . The phySpanish clinical guidelines recommend to perform a genotypic drug resistance test before starting antiretroviral therapy (ART) in all HIV-1-diagnosed patients and in ART-failing cases . Pr-RT sThe Basque Country and Galicia are two regions located in northern Spain, comparable in terms of population and HIV-1 diagnosis rates. During 2013–2018, the mean resident population and rates of new HIV diagnoses were estimated in 2,2 million and 6,9 per 100,000 inhabitants for the Basque Country and 2,7 million and 5,6 per 100,000 inhabitants for Galicia . In thisSamples from individuals newly diagnosed of HIV-1 infection in the northern Spanish regions of Galicia and Basque Country during 2013–2018, sent to the HIV Biology and Variability Unit, Centro Nacional de Microbiología, Instituto de Salud Carlos III, were included in the study.The representativeness of the NDs of our cohort was estimated comparing them to the NDs reported to the Spanish information system on new HIV diagnoses  and CEI PI 31_2019-v5 (dated 6 November 2019). This study did not require written informed consent by study participants, except for those participants who required additional samples different from the ones obtained in the routine clinical practice.pol (HXB2 positions 2253–3629) was amplified by RT-PCR followed by nested PCR from RNA or by nested PCR from DNA. Reagents, PCR thermal profiles, and primers are described in Nucleic acid was extracted from plasma or whole blood samples. RNA was extracted from 1 ml plasma using NUCLISENS® easyMAG®  and DNA was extracted from 200 μl whole blood using QIAamp® DNA DSP blood mini kit , following the manufacturer’s instructions. A Pr-RT fragment of Population sequencing was performed with ABI Prism BigDye Terminator Cycle Sequencing kit and ABI 3730 XL sequencer  in the Genomic Unit of Instituto de Salud Carlos III. Sequences were assembled with SeqMan Pro v.12.2.1  and edited with BioEdit v.7.2.5 .pol sequences from the patients included in this study and sequences obtained by us from another 10,687 HIV-1-infected individuals attended in clinical centers from Spain whose samples were collected in the period 1999–2019 were included in the analyses. A single sequence per patient was used in the phylogenetic analysis. In cases where several sequences were available for one patient, that closer to the date of HIV-1 diagnosis was selected.Partial Reference sequences from the different subtypes and CRFs retrieved from the Los Alamos HIV Sequence DatabaseSequences were analyzed phylogenetically by an approximately maximum-likelihood method using FastTree2 , runningTransmission clusters were defined as those comprising viruses from four or more individuals, at least 50% of them Spanish, and whose sequences grouped in the phylogenetic tree with a SH-like node support value ≥ 0.95. This limit in the percentage of migrants included in TCs was used to minimize the effect of viruses which are circulating in the countries of origin of the migrants, grouping phylogenetically in TCs in our sequence dataset due to the relatedness of the viruses of those countries, although they are not actually spreading in Spain.p < 0.05. A multivariable logistic regression model was performed to identify factors associated to TCs. The model was adjusted by gender, age group, transmission route, country of origin of the patient, Spanish region of sample collection and HIV-1 genetic form. Associations were measured using the odds ratio (OR) and its 95% CI. Data analyses were performed using the STATA statistical software package Version 16 .To evaluate the association between variables, Chi-squared and Fisher’s exact tests were used, with associations being considered statistically significant at a value of To avoid the identification of transmission networks and the potential breech of patient confidentiality, only 19% of the sequences have been deposited in GenBank, including at least two sequences from each TC comprising five or more patients with new HIV-1 diagnoses in the period of study. The sequences are under the following accession numbers: KT276255, KT276260, KT276263-KT276264, KT276266-KT276267, KT276270-KT276271, KU685562-KU685565, KU685567, KU685569-KU685575, KU685577, KU685581-KU685582, KU685586, KU685588-KU685590, KU685592, KX534325, KX534329, KX534331, KY465968, KY496624, KY514084, KY989950, MF999250-MF999256, MF999258-MF999261, MK177721-MK177733, MK177735-MK177752, MK177754-MK177757, MK177761-MK177772, MK177783-MK17785, MK177787-MK177790, MK177792, MK177795-MK177796, MK177798-MK177799, MK177801-MK177803, MK177805-MK177807, MK298150, MT436242, MT436244, MT436246-MT436247, MT436249-MT436250, MW344920-MW344921, MW584217-MW584224, OK011532, OK011542, OK011545-OK011546, OK011549, OK148912, OK148914, OK148917-OK148919, OK148921, OK148941-OK148942, OK148953-OK148957, OK148961, OK148965, OK148968-OK148972, OK148974, OL982314-OL982315, and OM914651-OM914711.A total of 1,158 HIV-1 NDs from Galicia and Basque Country diagnosed in 2013–2018 were included in the study . The majSeventy percent of the patients were native Spanish , followep = 0.13). The percentage of patients of non-Spanish origin was 35% in the Basque Country (13% corresponding to Africans), a proportion which is statistically higher (p < 0.001) compared to the 17% found in Galicia (2.2% Africans). Statistical differences in the distribution of genetic forms were also observed between both regions (p < 0.001), with the frequencies of subtype F (13%) and CRF02_AG (9.9%) being higher in Galicia and the Basque Country, respectively .Fifty-one percent (594/1158) of the individuals belonged to 162 different TCs. Regarding regions, 45% (351/776) of the patients were included in 98 TCs in the Basque Country and 64% (243/382) belonged to 82 TCs in Galicia . EighteeNon-subtype B genetic forms were found in 33 (21%) of the 162 TCs identified in the study. Sixteen of them derived from genetic forms circulating in Latin America  and 10 from genetic forms circulating in Africa . Twenty-nine percent (138/474) of the Spaniards belonging to TCs were members of non-subtype B TCs.A total of 15 large TCs  were identified in the study , 10 of tA phylogenetic tree which includes all the TCs comprising five or more patients newly diagnosed in the studied period in Galicia and Basque Country is shown in p = 0.036). The age range of 20–29 years showed an increased percentage of patients in TCs (59%), which was especially high in Galicia  but was not statistical significant in the Basque Country, and no statistical differences were found in the distribution of main variables.The percentage of patients in TCs was higher in males (57%) than in females (22%), and in MSM (67%) than in heterosexuals (31%). This percentage was also higher in Spaniards (64%) than in Latin Americans (35%) or Sub-Saharan Africans (1.2%), and in individuals infected with viruses of subtypes F (76%) or B (58%) than in those infected with CRF02_AG viruses (17%). The different distribution of TCs according to gender, mode of HIV-1 transmission, country of origin of the patient, and HIV-1 genetic form were statistically significant . The ageAlong the studied period, there was no clear trend in the proportion of patients associated with TCs . In GaliIn the multivariate analysis, males  and MSM  had higher odds of belonging to a TC compared to females and heterosexuals, respectively . PatientIndividuals from Latin America , North Africa  and especially from Sub-Saharan Africa  were inversely associated to belonging to TCs compared to Spanish patients . SimilarThe phylogenetic analysis of sequences from almost 12,000 HIV-1-infected patients from our database has allowed us to investigate the transmission events occurring during the 2013–2018 period in two regions of northern Spain, Galicia and Basque Country, identifying TCs and their associated factors. Our ND cohort had a good representativeness, corresponding to 64% of the NDs reported to the SINIVIH from these regions during that period, especially in the Basque Country where it reached 86%.Our analysis has assigned 51% of the NDs from Galicia and Basque Country to 162 different TCs, indicating that TCs are playing an important role in the spread of HIV-1 infections in both regions. There is no consensus on the criteria for defining a TC, as these should depend on the aim of the study . We consTransmission clusters were found associated with male gender and MSM. In fact, almost all the largest TCs (≥30 patients) identified in our study were associated with MSM. HIV-1 molecular epidemiological studies in different countries, independently of the methodology used, have found a similar association . Also, sIn Spain, 36% of HIV-1 infections diagnosed in 2019 were in migrants . MigrantDetermining the origin of HIV-1 infections in the migrant population would allow proper allocation of resources for preventive measures . PreviouWith regard to the role of immigration on the origin of HIV-1 TCs in Spain, it is also interesting to note that 21% TCs identified in this study are of non-subtype B genetic forms, with their ancestry showing some correlation with the predominant geographic origins of the immigrant population in Spain. Thus, the fact that 16 TCs derive from genetic forms circulating in Latin America and Africa may correlate to the high number of immigrants from these geographic areas living in Spain, representing around 36 and 18%, respectively, of the approximately 7.3 million immigrants . SimilarSubtype B was the most represented genetic form associated to TCs. Only subtype F infections (76% of NDs in TCs) showed a higher frequency than subtype B infections (56% of NDs in TCs) of belonging to TCs. This was mainly due to the presence of two large TCs of F1 subsubtype, designated F1_1  and F1_3 , which have spread among MSM mainly in Galicia and Basque Country, respectively , 2019. IIn general, there was not a clear temporal trend in the proportion of patients belonging to TC, although in Galicia our data show an increase in the proportion of patients in TCs in the last years. However, trends are difficult to evaluate due to the presence of fast-growing TCs in some periods.A different distribution of TCs is responsible for the spread of HIV-1 in Galicia and the Basque Country. Large MSM TCs have spread locally in both regions and the majority of the identified TCs were associated with this population group. However, we found a higher frequency of TCs associated with PWID or heterosexual transmission in Galicia. Galician patients have 1.5 higher odds of belonging to TCs than individuals from the Basque Country. This can be related to the low percentage of migrants in Galicia, who have a reduced association to TCs, and the high number of patients belonging to the large F1_1 TC, currently comprising 205 individuals, which has successfully spread in Galicia and other Spanish regions , even inIn this study, we have shown that MSM TCs are a keystone of the HIV-1 epidemic at regional and probably also at the country level, according to the propagation of the large MSM TCs identified in this study in different regions of Spain. Consequently, reinforcement of public health measures for preventing HIV-1 infections in MSM, such as behavioral interventions to reduce risky practices, pre-exposure prophylaxis , and earImplementation of preventive public health measures targeting MSM could reduce indirectly the spread of HIV-1 in Spain, which is mainly MSM-driven, in other population groups. National surveillance data in the United States suggest that infections among heterosexual women predominantly originate from MSM . MoreoveThe high representativeness of our cohort, especially in the Basque Country, suggests that the largest and most spread TCs in these regions have been identified, which supports the conclusions of the study. However, our data may have some limitations as some of the NDs from Basque Country and Galicia during the studied period were not analyzed and not all the TCs propagating in Spain were detected in our phylogenetic analysis.Our study has provided valuable data on the HIV-1 epidemic in Spain, identifying specific features at geographical and population levels for tailoring more specific public health interventions. The implementation of a molecular HIV-1 surveillance system to monitor the evolution of the epidemic in Spain could allow to promptly detect rapidly expanding TCs needing urgent investigation and the implementation of additional public health measures to prevent their spread , as wellBasque Country: Hospital Universitario de Araba, Vitoria: Andrés Canut-Blasco, José Joaquín Portu, Carmen Gómez-González; Hospital Universitario de Basurto, Bilbao: Josefa Muñoz, Mª Carmen Nieto, María Zuriñe Zubero, Silvia Hernáez-Crespo, Estibaliz Ugalde; Hospital Universitario de Cruces, Barakaldo: Luis Elorduy, Elena Bereciartua, Leyre López Soria; Hospital de Galdakao: Mª José López de Goicoechea, José Mayo; Hospital Universitario Donostia: Gustavo Cilla, Julio Arrizabalaga, José Antonio Iribarren, Mª Jesús Bustinduy, Mª Julia Echevarría. Mª Yolanda Salicio, David Grandioso. Galicia: Área sanitaria de Ferrol: Ana Mariño, Patricia Ordóñez, Hortensia Álvarez, Nieves Valcarce; Complejo Hospitalario Universitario de A Coruña: Ángeles Cañizares, Mª Ángeles Castro. Hospital Universitario Lucus Augusti, Lugo: Ramón Rabuñal-Rey, María José García-País, Mª José Gude-González, Pilar Alonso-García, Antonio Moreno-Flores; Complejo Hospitalario Universitario de Ourense: Juan García Costa, Ricardo Fernández-Rodríguez, Raúl Rodríguez-Pérez, Jorge Guitián, María Dolores Díaz-López, María Genoveva Naval-Calviño; Complejo Hospitalario Universitario de Vigo: Celia Miralles, Antonio Ocampo, Sonia Pérez-Castro, Jorge Julio Cabrera; Complejo Hospitalario Universitario de Pontevedra: Julio Díz-Arén, Matilde Trigo, Mª Ángeles Pallarés. Navarra: Complejo Hospitalario de Navarra, Pamplona: Carmen Ezpeleta Baquedano, Carmen Martín Salas, Irati Arregui García, María Gracia Ruiz de Alda. Madrid: Centro Sanitario Sandoval, Madrid: Jorge del Romero, Carmen Rodríguez, Mar Vera, Óskar Ayerdi, Eva Orviz; Hospital Universitario de Fuenlabrada: María Isabel García-Arata, Santiago Prieto-Menchero; Hospital Clínico Universitario San Carlos, Madrid: Esther Culebras, Icíar Rodríguez-Avial; Hospital Universitario Fundación Jiménez Díaz, Madrid: Raquel Téllez-Pérez, Olalla Calabia-González, Alfonso Cabello-Úbeda, Miguel Górgolas Hernández-Mora; Hospital Universitario Severo Ochoa, Leganés: Sara María Quevedo, Lucía Puente, Manuel del Álamo; Hospital Fundación Alcorcón, Madrid: Carolina Campelo Gutiérrez, María José Goyanes Galán; Castilla y León: Hospital Clínico Universitario de Valladolid: Carmen Hinojosa, Carlos Dueñas, Begoña Monteagudo, Edita Sánchez; Hospital Río Hortega, Valladolid: Jessica Abadía, Belén Lorenzo Vidal; Hospital Virgen de la Concha, Zamora: Teresa Martín-Domínguez, Rosa Martínez-González. La Rioja: Hospital San Pedro, Logroño: José Ramón Blanco, Miriam Blasco. Aragón: Hospital Universitario Miguel Servet, Zaragoza: Ana María Martínez-Sapiña, Piedad Arazo. Castilla-La Mancha: Hospital Universitario de Guadalajara: Alejandro González Praetorius, Complejo Hospitalario de Toledo: César Gómez-Hernando, José Largo-Pau; Comunitat Valenciana: Hospital Universitari Sant Joan d’Alacant: Fernando Buñuel, Ana Infante.https://www.ncbi.nlm.nih.gov/genbank/, KT276255, KT276260, KT276263-KT276264, KT276266-KT276267, KT276270-KT276271, KU685562-KU685565, KU685567, KU685569-KU685575, KU685577, KU685581-KU685582, KU685586, KU685588-KU685590, KU685592, KX534325, KX534329, KX534331, KY465968, KY496624, KY514084, KY989950, MF999250-MF999256, MF999258-MF999261, MK177721-MK177733, MK177735-MK177752, MK177754-MK177757, MK177761-MK177772, MK177783-MK17785, MK177787-MK177790, MK177792, MK177795-MK177796, MK177798-MK177799, MK177801-MK177803, MK177805-MK177807, MK298150, MT436242, MT436244, MT436246-MT436247, MT436249-MT436250, MW344920-MW344921, MW584217-MW584224, OK011532, OK011542, OK011545-OK011546, OK011549, OK148912, OK148914, OK148917-OK148919, OK148921, OK148941-OK148942, OK148953-OK148957, OK148961, OK148965, OK148968-OK148972, OK148974, OL982314-OL982315, and OM914651-OM914711.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: The studies involving human participants were reviewed and approved by Bioethics and Animal Well-being Committee of Instituto de Salud Carlos III. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.HG, ED, and MT conceived the study and supervised the experimental work. ED, HG, MT, and JC-G processed sequences and performed phylogenetic analyses. HG and ED performed data curation. HG, AD, and LG performed statistical analyses. SB, MS, VM, and EG-B performed experimental work. The members of the Spanish Group for the Study of New HIV Diagnoses recruited patients and obtained epidemiological and clinical data. HG wrote the manuscript draft, with contributions to the text by AD, MT, and ED. All authors contributed to the article and approved the submitted version.This work was funded through Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, Project “Estudios sobre vigilancia epidemiológica molecular del VIH-1 en España,” PI16CIII/00033 and Project “Epidemiología molecular del VIH-1 en España y su utilidad para investigaciones biológicas y en vacunas“PI19CIII/0042; Red de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Subdirección General de Evaluación y Fondo Europeo de Desarrollo Regional (FEDER), Plan Nacional ICDCI, project RD16ISCIII/0002/0004; and scientific agreements with Consellería de Sanidade, Government of Galicia (MVI 1004/16), and Osakidetza-Servicio Vasco de Salud, Government of Basque Country (MVI 1001/16).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The initial software fitting prescribed by the fitting formula largely depends on the patient's hearing loss, which may not be the optimal preference for a particular user. Certain criteria must also be readjusted by an audiologist to meet the user-specific requirements. Therefore, this study focuses on the novel application of a neural network (NN) technique to build a suitable fitting algorithm with prescribed hearing loss and the corresponding preferred gain to minimize the gap between optimized fittings. The algorithm intended to learn the hearing preferences of an individual user such that the initial fitting may be optimized. These findings demonstrate the efficiency of the algorithm, with and without additional features. Using the clinical fitting data, the average mean square error (MSE) for the simple NN algorithm was 5.4183%. By adding additional features to the data, the algorithm performed better, and the average MSE was as low as 5.2530%. However, the algorithm outperformed Company A fitting software, as the MSE was the highest at 5.4748%. As the company's automatic fitting has a noticeable discrepancy with clinical fitting records, the impeccable results from this study can lead to a better path towards fitting satisfaction, thus benefiting the hearing-impaired community to a larger extent. For patients with hearing loss, good hearing aid fitting is more than just choosing an effective hearing aid (HA) device. Hearing aid fitting formulas calculate the amount of electroacoustic amplification required for people with hearing loss . Modern The National Acoustic Laboratories' (NAL) nonlinear (NL) fitting procedure, NAL-NL1 , 6, NAL-It has been acknowledged that up to 50% of hearing aid users prefer amplification or compression settings different from those recommended by the manufacturer –11. ThisThe dynamic range (DR), the long-term average speech spectrum (LTASS), and the band importance function (BIF) of speech are the most substantial features of language in terms of acoustics and linguistic attributes . TherefoOnly a few studies have reported strategies for self-adjustment or self-tuning compression in HA fitting –22. HoweTherefore, the purpose of this study was to develop a personalized hearing aid fitting method for Korean users and to compare the differences in gain preferences between the initial fitting of HA devices. We used fitting data for the products of a well-known hearing aid company, which accounts for more than 20% of the global market and distributes its hearing aids through hospitals in Korea. In this study, the hearing aid company will be referred to as Company A. First, the preferred gain for the HA fitting is compared with the initial fitting of Company A. Second, an NN-TL approach is used to predict the preferred HA fitting of hearing loss patients with and without additional features to learn if additional features such as age, sex, or ear type help to obtain better results. In general, this study will provide information on whether HA fitting formulas need to be specific to the native language of the HA user, and additional features will help the algorithm learn better.The remainder of this paper is organized as follows: Many variables related to hearing aids and patient conditions affect hearing aid outcomes. The current study considered only some specific conditions, including patients with sensorineural hearing loss, user experience in HA, behind-the-ear (BTE) HA, 2 cc couplers, and 6 channels when insertion gains were determined for each frequency. The rationale of fitting was to make loudness comfortable while providing sufficient audibility for low (50 dB sound pressure level (SPL)), medium (65 dB SPL), and high (80 dB SPL) sounds.Clinical fitting data from 978 Korean patients (466 men and 512 women) with mild-to-severe sensorineural hearing loss were used in this study. Data were collected from the Department of Otolaryngology at Inha University Hospital, and no personal information regarding the participants was disclosed.The ages of the patients ranged from 1 to 96 years, and the distribution is shown in A simple block diagram of the proposed hearing aid fitting model is shown in Typically, fitting formulas calculate the insertion gain based on the user's hearing loss information. Here, we added some additional features as shown in the block diagram to feed the neural network model to compute the personalized insertion gain.A preliminary study on a machine learning approach to hearing aid fitting prescriptions was conducted using data from fitting software (NAL-NL1 and NAL-NL2) , and theInstead of random weight initialization, we retained the final weights of the NN model from our previous research  and usedThis experiment uses 900 clinical data for training and 78 clinical data for testing purposes. The training dataset and the test dataset were split with a ratio of 23 : 2. The datasets were selected randomly in such a way that no data appear more than once in the combined training and test sets. The training data are fed into the model in small batches. The ML approach uses training data to construct the mapping function between the result variable and the predictors, while testing data are used to evaluate the trained model's ability to predict the outcome variable.∗7 bit binary conversion∗6 positions) as shown in The dataset contained information on hearing loss at 6 different frequencies for each participant. In addition to hearing loss and insertion gain information for the corresponding loss, the dataset also contained additional features, such as age, gender, and ear type. We performed a binary conversion of hearing loss data and additional features as preprocessing and then positioned them based on the frequency hierarchy to create more features The performance of the algorithm for 3 different input levels  for initial fitting by Company A, clinical fitting, and NN fitting with and without additional features is shown in Figures 6To evaluate the algorithm's performance of predicting fitting records, we employed the mean square error, a commonly used error measure in the literature. A lower value is preferred for the measure, indicating a lower prediction error. The predicted MSE values are listed in The average MSE for the algorithm was 5.4183%, whereas using additional features, it was 5.2530%. However, the proposed algorithm outperformed the Company A fitting record. It was noticed that the company's automatic fitting has a big difference with real clinical fitting. Although the difference in MSE does not seem great, considering data discrepancy between the groups, the result is impeccable and may have a big effect on hearing aid systems. Moreover, this smaller contribution could show a better path for big companies, thus benefiting the hearing-impaired community to a larger extent. Software fitting is closer to ideal situations where very small or no difference is expected.Fortunately, all sophisticated modern fitting techniques provide hearing-impaired ears with at least some corrective gain. The ideal fitting approach, which has yet to be devised, would aim to restore all dynamic acoustic characteristics lost due to cochlear and conductive reasons. On the other hand, each patient is treated as a separate experiment with varying and unpredictable results. However, to develop a more precious algorithm, more clinical fitting data should be collected. Overcoming privacy concerns and different approval for data is tedious.Consequently, the insertion gain computed using the fitting formulas may not be the best gain for patients with hearing loss, and there is no possible baseline for a reasonable prediction error. The desired gain may differ significantly from one subject to another, from male to female, from young to elderly, or from one geographical location to another. Furthermore, we do not know how each fitting program calculates the insertion gain for corresponding hearing loss information. Therefore, this remains a black box.The use of linguistic characteristics in HA fitting is not a new concept. The tonal language was taken into consideration, and low-frequency gains were boosted when NAL-NL2 was created . HoweverWe attempted to bridge the gap between fitting satisfaction and hearing loss patient satisfaction by combining this technique with clinical data from an audiologist. Due to regulations and privacy concerns, collecting significant amounts of hearing aid fitting data from audiologists is a tedious task. Therefore, we considered the parameter transfer learning approach so that we could deal with the problem of smaller datasets. The prediction error for the insertion gain is basically the calculated difference between the predictive gain and the initial gain from the fitting formula. Therefore, a very small difference or no difference is expected under ideal conditions. We developed a fitting algorithm using the machine algorithm, and it is better than the company's fitting algorithm. However, to develop a more precious algorithm, more clinical fitting data should be gathered and the characteristics of the components (mic and rec) of the hearing aid should also be considered.The current study showed both limitations and possibilities for the effects of a language-specific HA fitting formula. In this study, the NN fitting model with improved hyperparameters enabled computational prototypes with many processing layers to learn data representation at several levels of abstraction, while the TL method accelerated training and improved model performance even with a smaller dataset. However, combining hearing aid fitting data collected from healthcare professionals with additional information, such as the patient's own choice of hearing aid type, age, and sex, provides a more realistic impression about the performance of the proposed algorithm. Both the simulation and experimental results demonstrated the effectiveness of the algorithm in achieving preferred hearing outcomes.


To analyze and compare the characteristics of macular morphology and microcirculation in diabetic macular edema (DME) patients with and without macular serous retinal detachment (SRD).One hundred eyes in 81 patients diagnosed with the DME  of ≥ 300 μm) from March 2020 to November 2020 were selected. According to whether complicated with SRD, patients were divided into DME with SRD (60 eyes) and without SRD (40 eyes) groups. We analyzed the following parameters: CMT, central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), number of hyperreflective foci (HF) in the complete retina, inner retina, outer retina, and subretinal space, the integrity of the ellipsoid zone (EZ) and external limiting membrane (ELM), the presence of disorganization of inner retinal layers (DRIL), foveal avascular zone (FAZ) area, and the vascular flow density of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris.P < 0.05) and a smaller CRT (P < 0.001); (2) The number of the HF in the complete retina, outer retina, and the subretinal space was larger in the group with SRD (P < 0.001); 3.The proportion of the EZ disruption (P < 0.05) and ELM disruption (P < 0.001) were higher in the group with SRD; 4. The SFCT (P < 0.05) and the vascular flow density of choriocapillaris (P < 0.05) were greater in the group with SRD; 5. There were no significant differences in the FAZ area and the vascular flow density of the DCP and SCP (P > 0.05); 6. The presence of the SRD was correlated with the integrity of the ELM, the number of HF in the complete retina, outer retina, and subretinal space , as well as the SFCT .(1) Compared to the group without SRD, the group with SRD had a greater CMT (The results support the hypothesis that the presence of the ELM disruption, the larger number of the HF, and the thickening and hyperperfusion of the choroid may be involved in the pathogenesis of SRD in DME. Diabetic macular edema (DME) is a complication of diabetes and one of the major causes of vision loss in patients with diabetes mellitus (DM) . This coBased on the morphology acquired from the optical coherence tomography (OCT), the DME exhibits the following structural changes: sponge-like diffuse retinal thickening (SDRT), cystoid macular edema (CME), and serous retinal detachment (SRD). On the OCT images, the SRD was manifested as an opaque dark area of fluid between the neurosensory retina and the retinal pigment epithelium (RPE), which accounts for approximately 15–30% of DME patients . TherefoOptical coherence tomography angiography (OCTA) is a safe and quick noninvasive approach to obtain images of vessels of the retina and choroid in situ. The OCTA quantitatively evaluates the different layers of the retinal capillary network, which offsets the disadvantages of using fundus fluorescein angiography (FFA) in the evaluation of the flow in the DR and DME. Hence, a standard of reference can be established for disease evaluation and prognostic prediction. Therefore, the present study aimed to analyze and compare the characteristics of the macular morphology and microcirculation by OCTA in two types of DME eyes: a group with SRD and a group without SRD. Further, this study planned to evaluate the characteristics of the DME eyes with SRD carefully to dissect out the pathogenesis of SRD.Informed consent was obtained from each patient, and the research was carried out in compliance with the Declaration of Helsinki principles. The patients with the DME were retrospectively assessed from March 2020 to November 2020 from the records in the Ophthalmology Department of Subei People’s Hospital . The stages of pre-proliferative diabetic retinopathy (PPDR) or proliferative diabetic retinopathy (PDR) were determined by FFA, and the DME was established by the OCT/OCTA examination. The DME was defined as a central retinal thickness of ≥ 300 m with the presence of intraretinal or subretinal fluid within the range of 1 mm of the macular fovea . The excThe systemic characteristics of patients, including sex, age, diabetic duration, the value of blood glucose (GLU), glycated hemoglobin A1c (HbA1c), and creatinine were evaluated.2 of the fovea to the scanning area. The FAZ area was denoted as the non-vascular region surrounded by the continuous capillary plexus of the retina. The vascular flow density of choriocapillaris was categorized as the ratio of the flow area within a diameter of 2 mm centered on the fovea to the scanning area.All patients were subjected to scanning by OCT and OCTA . The CMT, defined as the average distance between the inner limiting membrane of the retina and the RPE within 1.0 mm of the macular fovea, was computed using OCT mapping software. The heights of the SRD and central retinal thickness (CRT) were measured in the group with SRD , whereas the measurement data that did not conform to the normal distribution are expressed by the median . The measurement data were analyzed by independent t-test or non-parametric rank-sum test, and the counting variables were verified by the chi-square test. According to the data type, the chi-square test, logistic regression analysis, and the Spearman correlation analysis were performed for the correlation analysis. P-value of < 0.05 was considered to define statistically significant differences.All statistical analyses were performed using the SPSS software, version 25.0 . The measurement data were tested for normality. Continuous variables are presented as mean P > 0.05). In the 60 eyes with SRD, there were 40 eyes (66.7%) in the stage of PPDR and 20 eyes (33.3%) in the stage of PDR. Of the 40 eyes without SRD, 28 eyes (70.0%) were in the stage of PPDR and 12 eyes (30.0%) were in the stage of PDR. There was no significant difference in the proportion of PPDR and PDR between the two groups , course of diabetes, HbA1c, and creatinine between the two groups (P = 0.002) and SFCT [ (296.75 ± 53.41) µm vs. (271.83 ± 56.66) µm]  between the group with SRD and the group without SRD. On the other hand, the CRT of 403.00  µm in the group without SRD was larger than that in the group with SRD [294.05  µm] (P < 0.001) .There were statistically significant differences in terms of CMT [487.00  µm] vs. [403  µm] ; ELM disruption: (81.7%) vs. (30.0%), . The DRIL occurrence in the group without SRD (87.5%) was significantly higher than that in the group with SRD (60.0%),  .The proportion of the EZ and ELM disruption in the group with SRD was significantly higher than that in the group without SRD. EZ disruption: (96.7%) vs. (82.5%), . There was no significant difference in the number of the HF in the inner retina between the two groups .The numbers of the HF in the full retina [10.00 ], the outer retina [3.00 ], and the subretinal space [1.00 ] were larger in the group with SRD than in the group without SRD, which were 5.50 , 0.00 , 0.00 , respectively  than that in the group without SRD (50.81% ± 5.28%)  was significantly greater . The presence of the SRD was significantly correlated with the number of the HF in the complete retina, the outer layer, and the subretinal retina  but was not correlated with the number of the HF in the inner retina . There was a significant correlation between the presence of the SRD and SFCT . In the DME eyes with SRD, the height of the SRD was correlated with the number of the HF in the complete retina and outer retina . No significant correlation was found between the height of SRD and the number of the HF in the subretinal space, as well as the SFCT  (Table The ELM was intact in 11 eyes 18.3%) but disrupted in 49 eyes (81.7%) in the group with SRD (60 eyes). On the other hand, of 40 eyes without SRD, the ELM was intact in 28 eyes (70.0%) but disrupted in 12 eyes (30.0%). The SRD was significantly correlated with the integrity of the ELM . Besides, there was a significant correlation between the presence of the SRD and the integrity of the ELM.The ELM was considered a barrier restricting the movement of macromolecules formed by the bridging connection between the adjacent photoreceptors and the Müller cells. The ELM limited the migration of the exudated lipids, proteins, and other macromolecules from the inner layer of the retina to the outer layer . Some scRecently, increasingly more attention has been paid to the role of the HF from the OCT images as an imaging biomarker in vitreoretinal diseases. The HF was believed to be the product of lipid exudation after the destruction of the blood-retinal barrier . Other eThe EZ corresponds to the ellipsoid of the inner segment of the photoreceptor cell, which is rich in mitochondria. Thus, the disruption of the EZ affects the energy supply of the photoreceptor cells and hence the visual function. The DRIL is a structural disorder of the inner retina. Previous studies have confirmed that the FFA showed macular ischemia in the corresponding region of the DRIL. In recent years, many investigations have shown that the disruption of the EZ and the presence of the DRIL could be used as the major indicators of the visual outcome in the DME , 22. In In this study, by comparing the parameters of macular morphology and microcirculation of the DME patients with and without SRD, we found that the disruption of the ELM, the larger number of the HF, and the thickening and hyperperfusion of the choroid may have been related to the formation of the SRD in the DME. These current findings contribute to the existing understanding of the pathogenesis of the SRD in DME eyes.


It has been consistently reported that deaf individuals experience mathematical difficulties compared to their hearing peers. However, the idea that deafness and early language deprivation might differently affect verbal  vs. visuospatial  arithmetic performances is still under debate. In the present paper, three groups of 21 adults  were therefore asked to perform, as fast and as accurately as possible, subtraction and multiplication operations. No significant group effect was found for accuracy performances. However, reaction time results demonstrated that the deaf group performed both arithmetic operations slower than the hearing groups. This group difference was even more pronounced for multiplication problems than for subtraction problems. Weaker language-based phonological representations for retrieving multiplication facts, and sensitivity to interference are two hypotheses discussed to explain the observed dissociation. A converging body of evidence in the numerical cognition field suggests that different arithmetic operations rely on distinct neuro-cognitive processes. Indeed, while subtraction is solved using visuospatial procedures  and visuWhen taking the link that exists between language skills and arithmetic processing into account, it is not surprising to see that deaf individuals, who often experience some level of language deprivation in early childhood, present poorer numerical abilities than their hearing peers see  has indeThese observations were interestingly assumed to be caused by some linguistic aspects . In contAs a close correlation between phonological awareness and arithmetic problem solving has also been repeatedly observed , the parTo do so, we will ask Belgian deaf signers, hearing signers and hearing controls to perform easy and difficult subtraction and multiplication operations. In Belgium, there are few options regarding education of deaf children. First, there exists the special-need education schools, but sign language is not provided as instruction language since the teachers are often hearing and using spoken language. Second, there is the regular school system with the presence of a sign language interpreter. However, the deaf child has to be confident with sign language before he/she can benefit from “translated” classes. A third and last option is the bilingual-bicultural education, which offers deaf children all the opportunities to get into contact with both spoken and signed languages, and both cultures. Unfortunately, not many schools provide this educational system in Belgium. Many Belgian deaf signers therefore consider sign language as their preferred communication method but were taught arithmetic in another spoken language. Including hearing signers in this study will therefore allow us to examine whether the arithmetic difficulties experienced by deaf signers are merely linked to the use of sign language or to the use of sign language as mother tongue (L1) while being taught arithmetic in a second spoken language (L2: Dutch or French). As several studies already demonstrated that unimodal bilingualism can impact number and arithmetic processing , there iFinally, as recent behavioural ,b and brTo sum up, our study aims to investigate whether the arithmetic deficit in deaf individuals is: (1) global, or more specifically related to verbal numerical operations ; (2) linked to auditory deprivation, language deprivation, the mere use of sign language or the use of sign language as L1 while being taught arithmetic in a spoken L2 (Dutch or French that might not have been fully accessible despite the use of hearing aids); and (3) linked to the interference index of single-digit multiplication problems. If the arithmetic difficulties of deaf adults are global, their performance should be worse than the one of the hearing signers and hearing controls in both arithmetic operations. If deafness and its related language experience more strongly affects verbal operations, the difference between the deaf and the hearing adults should be bigger for the multiplication operations. Finally, as hearing signers were taught arithmetic in their mother tongue , their later acquisition of sign language should not affect their arithmetic performances. They should therefore behave exactly as the hearing controls.X2  = 2.19, p = 0.33], age , educational level , handedness , and mother tongue (French vs. Dutch) . Hearing signers reported a minimum level of B1  for sign language , a group of hearing signers , and a control group of hearing adults who did not know sign language   on a grey background. Each category of operations consisted of 20 problems to solve: some easy operations  and some difficult operations . Accuracy scores and reaction times (in ms) were measured. A binary Generalised Linear Mixed Model (GLMM) was run on accuracy scores (correct or not correct). A GLMM was run on the reaction time data (only reactions times for correct answers were included), indicating gamma distribution. One random factor was included in all analyses because of its significant contribution to the variance . The fixed factors included Group , Operation  and Level , as well as their interactions. Given that deaf adults often experience executive functioning difficulties due to language deprivation, we hypothesised that our deaf group might be more sensitive to interference. To investigate if deaf individuals are indeed more affected by the interference index of single-digit multiplication problems, we performed a GLMM indicating gamma distribution with Group, Interference index and its interaction as fixed factors, and reaction time as dependent variable. Interference indexes were taken from Statistical analyses were carried out using IBM SPSS statistics 26 software for Mac OS Monterey 12.0.1 . Statistical significance was set at Operation  or Group  was shown. Nevertheless, a significant main effect of Level  and a significant Level x Operation interaction was observed . The Group × Operation , Group × Level , and Group × Operation × Level  interactions were not significant. The final GLMM was run with the only significant interaction included and led to the same conclusion: Significantly higher accuracy scores were observed for the easy operations  compared to the difficult operations . A significant difference between subtraction problems and multiplication problems was found for the easy operations only, where the accuracy scores of multiplication problems were lower  than those for subtraction problems  (see A binary GLMM was run on the accuracy scores as described above. No main effect of 025) see .Operation , Group , and Level . No significant Group × Level interaction  and no Group × Operation × Level interaction  was seen. However, significant Group × Operation  and Operation × Level  interactions were observed. The final GLMM was run including the two significant interactions and led to the same conclusion: Subtraction problems  were solved faster than multiplication problems . Deaf adults  were slower than hearing signer adults , and hearing control adults . Hearing signers did not perform differently compared to hearing controls (p = 0.33). Responses to difficult operations were slower  than responses to easy operations . The difference between deaf  and hearing signers  as well as between deaf and hearing controls  was bigger for the multiplication problems than for the subtraction problems. The difference between subtraction problems and multiplication problems was only found for the difficult operations , and not for the easy ones   see . Similar.13) see . MoreoveGroup , and Interference index  was observed together with a significant Group × Interference index interaction . Deaf  performed slower than hearing signers , p = 0.011, and hearing controls , p = 0.001 . Hearing individuals may not prevent themselves from relying on the phonological aspects of the presented stimuli, while deaf signers may experience some issues in accessing the verbal associations of multiplication facts. This hypothesis is, however, speculative and should be further tested in the future.Recent years have seen a surge in empirical studies examining the role of language in accounting for cross-language disparities in children’s number understanding and arithmetic competence . It has  systems , which gper se or from a delay in accessing and mastering verbal or visual languages.As the control groups (hearing controls and hearing signers) have experienced typical language development with typical language access from birth, they differ from the deaf group in language modality and in hearing status but also in early language access. This delay in accessing language can therefore be the main factor subtending the arithmetic difficulties of our deaf sample. Signed languages are indeed complete, natural languages that consist of their own unique visual grammar and syntax . ConsistWhile To conclude, our findings are in line with several previous studies suggesting that deaf individuals have no deficits in their numerical representation of magnitude information , but might experience a less efficient processing  of basic numerical information . This leThis study investigated how deafness and its related variable language experience, including language deprivation, shapes verbal vs. visuospatial arithmetic performances. Although the accuracy scores between deaf signers, hearing signers and hearing controls did not differ, the deaf signers showed significantly slower reaction times compared to the two hearing groups. Importantly, this significant group difference was larger for multiplication operations than for subtraction operations. These findings support the idea that numerical tasks relying on verbal processes are more strongly impacted by deafness and its following language experience, compared to numerical tasks implying visuospatial processes . FurtherThe raw data supporting the conclusions of this article will be made available by the authors, upon request to the corresponding author.The studies involving human participants were reviewed and approved by the “Comité d’Ethique Hospitalo-Facultaire Saint-Luc-UCLouvain” (2019/19AOU/357). The patients/participants provided their written informed consent to participate in this study.MB: conceptualisation, methodology, software, formal analysis, investigation, data curation, visualisation, writing – original draft and review, and editing. VC: conceptualisation, methodology, software, writing – review and editing, supervision, validation, project administration, and funding acquisition. Both authors contributed to the article and approved the submitted version.


Difficulty understanding speech, particularly in situations unfavorable to communication, is a common complaint among elderly individuals.To verify the variables connected to hearing loss and stimulus presentation rate and their impact on the speech recognition skills of elderly subjects in quiet and noisy environments.This case-control study included two groups of subjects  exposed to the List of Sentences in Portuguese and the Slowed List of Sentences in Portuguese tests. Sentence recognition indices were calculated for tests done against noisy and quiet backgrounds at a normal and reduced speech rate. Data sets were submitted to statistical analysis.elderly subjects from both groups had better test results when sentences were played at a slower rate. Statistically significant difference was seen for both groups when the tests were carried out on a quiet background and for the group with hearing loss when tested on a noisy background.regardless of their peripheral hearing, the elderly subjects included in this study were more able to recognize speech when sentences were played at a slower rate against a quiet background. When sentences were played against a noisy background, the elderly subjects with hearing loss had more significant performance improvements than the ones with normal hearing when sentences were played at a slower rate. Interest has grown around the issues connected to aging and temporal auditory processing. Elderly subjects without hearing loss have reported difficulty detecting lower intensity sound stimuli and understanding speech, particularly in situations in which competing sound stimuli are present, while others with hearing loss sometimes fail to present similar complaintsThe rapid sequence of connected sound stimuli characteristically seen in speech may be overwhelming to subjects with impaired temporal auditory processing, who end up missing brief but relevant bits of acoustic information required for effective communication to occurDifficulty understanding speech is a common complaint among elderly subjects, particularly in contexts unfavorable to communication, such as when speech is delivered at a faster rateCommunication deficits have been reported by elderly individuals with and without hearing lossTraditional tests used to evaluate temporal auditory processing skills resort to non-verbal stimuli; however, these tests are known for not completely assessing one's ability to understand speech. Sentence-based speech recognition tests, by their turn, closely emulate situations of everyday lifeThis study aimed to determine the influence of variables hearing loss and speech rate in the elderly, against quiet and noisy backgrounds.o. 029 457. The study was approved by the Research Ethics Committee of an institution of higher education and given permit 0098.0.243.000–11. The study was carried out in the Laboratory for Hearing Aids of the Speech and Hearing Therapy Service of a higher education institution.This study is linked to project ‘Sentence recognition at different speech rates’ registered in the Project Department of the Center for Health Sciences under nAll subjects were informed of the objectives, rationale, benefits, risks, and research procedures; participants were given access to ample clarification; participant identities and data were guarded by the researcher and treated confidentially; participants were given permission to leave the study at any time for any reason; participants were offered direct access to the examiner in person or by phone when they thought necessary.Data was contained in the informed consent term, which was duly read and signed by those who agreed to participate in the study.The group of elderly subjects with normal hearing (control group) was made up of individuals coming from associations of seniors, while the group of subjects with hearing loss (case group) had elderly citizens awaiting for hearing aids granted by a federal program managed by the Institution and some individuals from associations of seniors.The enrollment criteria included: age over 60 years ; having a Percentage Speech Recognition Index (PSRI) of 72% or above; no outer ear involvement; no history of alterations or deficits that could compromise the execution of the test procedures ; and/or noticeable speech disorders.Additionally, subjects in the control group had to have auditory thresholds within normal limits - tritone average equal to or less than 25 dBBefore they were divided into groups, the volunteers were interviewed, had their outer ear canals inspected, underwent pure-tone audiometry (PTA) at 250–8000 Hz for air conduction and 500–4000 Hz for bone conduction, had their Speech Recognition Thresholds (SRT) determined for disyllables, and their Percent Speech Recognition Indices (PSRI) for monosyllables in a soundproof booth, using a two-channel digital audiometer (Interacoustics Affinity AC440) and Telephonics TDH-39P earphones.The group of normal hearing elderly (control group) consisted of 31 subjects, six males and 25 females, aged between 61 and 81 years. The group of elderly people with hearing loss (case group) had 26 subjects, 12 males and 15 females, aged 60 to 84 years. Fourteen subjects in the case group had mild sensorineural hearing loss in the better ear and 12 had moderate sensorineural hearing loss.After the subjects were split in groups, their Percent Sentence Recognition Indices in Silence (PSRIS) and Percent Sentence Recognition Indices in Noise (PSRIN) were obtained through the application of the List of Sentences in Portuguese - LSPThe LSPThe SLSPA new CD was produced to contain the eight tracks with the list of sentences from the original LSP, however with speech rate decreased beyond the range of the calibration pure tone, and background noise within the spectrum of speech included in the original CDTest measurements were made in a soundproof booth with the two-channel digital audiometer described above, in addition to an amplifier equipped with Iridium PA100 speakers for free field measurements.The calibration of the equipment for free field measurements was carried out on the place where the patients would be positioned, i.e., one meter away from the speakers at 0°, 0° azimuth, by a trained expert registered at Inmetro São Paulo. Sound pressure level (SPL) measurements were made using the meter's fast-response A scale, as it is the one that most closely matches the human auditory response, in addition to being used by most researchers in this area.Open field measurements were monitored throughout the study by the examiner with the aid of a RadioShack digital sound pressure meter, considering the characteristics of the test signal and the need to always maintain the same acoustic conditions in the environment.The reference pure tone present in the first track of the CD was used to establish the calibration parameters of the channel in which the sentences were played, thus ensuring consistent speech stimuli reproduction.Noise was used as the reference in the calibration of the noise present in the other channel of the CD, as it is a continuous sound. The output of each channel was calibrated using the audiometer's VU-meter. The pure tone in channel one and the noise in channel two were set at zero.The sentences and noise recorded on the CD in independent channels were played on a Toshiba 4149 CD player coupled to the described audiometer and speakers.Measurements were made in the following order: SRTSSS, PSRISSS, PSRIS, SRTSSN, PSRISSN, and PSRIN. Patients were trained to become familiarized with the test protocol before measurements were made.Sentences 1 to 5 on slowed sentence list 1A were played against a quiet background to capture SRTSSS, PSRISSS and PSRIS.In addition to familiarizing subjects with the test, training also served to determine the necessary initial intensity of sentence presentation so that the subjects could understand the first sentence on each of the test listsSpeech Recognition Thresholds of Slowed Sentences in Silence (SRTSSS) were determined using list 1B from the SLSP against a quiet background. Speech Recognition Thresholds of Slowed Sentences in Noise (SRTSSN) were obtained using list 4B from the SLSP against a background of noise.A sequential/adaptive or ascending/descending strategy was used in the verification of speech recognition thresholds of slowed sentencesIn this strategy, when subjects correctly recognized the speech stimuli, the intensity of presentation of the next sentence was reduced; and when they failed to recognize the speech stimuli, the intensity of presentation was increased. A response was considered correct only when the subject was able to repeat the entire sentence, without error or omissions.Stimuli were presented in intervals of 4 dB until the first change in the type of response; then the intervals were decreased to 2 dB until all sentences were played, as recommended in the literatureNoise intensity was kept at a constant 65 dB SPL (A) during the acquisition of SRTSSN.The acquired thresholds were used to determine the sentence list presentation parameters for the acquisition of percent sentence recognition indices.First, the Percent Sentence Recognition Index of Slowed Sentences in Silence (PSRISSS) was determined using list 2B from the set of slowed sentences (SLSP), followed by the Percent Sentence Recognition Index in Silence (PSRIS) assessed using list 3B of sentences played at a normal rate (LSP). The PSRISSN was obtained using list 5B in the SLSP, and the PSRIN was tested using list 6B in the LSP.The stimulus intensities found in the SRTSSS and SRTSSN tests were used to set up the sentence presentation parameters in the percent sentence recognition index tests in silence and noise, respectively. Noise intensity was kept at a constant 65 dB SPL (A) during the acquisition of SRTSSN and PSRIN.Indices were calculated based on word scoresIn this calculation method, two points are awarded for each content word  and one point for each functional word  correctly repeated. At the end of the presentation of the list, the total score is multiplied by a preset factor to yield the percent rate of correct responses, which will make up the individual's Percent Sentence Recognition Index.t-test was used to analyze the significance of dependent variables with a normal distribution; the Wilcoxon signed-rank test was used to treat variables that did not follow a normal distribution.The Lilliefors test was used to verify the normality of the variables; the p < 0.05).A level of statistical significance of 5% was considered  and elderly individuals with hearing loss (case group) showed statistically significant improvements in test scores when presented with slowed sentences, which showed that speech recognition in the subjects of both groups was improved when speech was produced at a lower rate.Our findings were compared against those of studies in which temporal auditory processing was mostly assessed through non-verbal stimuli, due to the difficulty finding studies in which speech stimuli were used to investigate the correlations between temporal auditory processing and speech recognition.Some authorsEvidence that the rate of speech affects the performance of elderly individuals has been reported in a studyThe analysis of the measurements carried out against a noisy background showed that control group subjects had no statistically significant differences in performance when test speech rates were changed. Nonetheless, significant improvement was observed in case group individuals performance when slowed sentences were played. This shows that being spoken to slowly is important for the elderly, particularly for individuals with hearing loss.Our findings show the importance of educating the families of the elderly, particularly those of individuals in need of wearing hearing aids, on the adoption of communication strategies such as speaking more slowly, so their dear ones can engage in fulfilling conversations. The importance of family education in attaining successful communications with the elderly has been reportedOur results also serve as a warning to health care workers, so that they can modulate their speech rate to meet the needs of elderly patients.Although the degree of audibility strongly influences speech recognition, some elderly subjects seem to face more difficulties than expected from the analysis of audiometric configurations. One of the difficulties in speech recognition of the elderly derives from the age-related decline in cognitive skills, changes in auditory processing, or the combination of bothAuthorsThe results of speech recognition tests in noise showed clear improvements in the performance of elderly subjects with hearing loss as the rate of speech was decreased, even in the absence of expected intonations or visual cues relied on by individuals to better understand what they hear in noisy environments. This shows how decreases in speech rate are really important for the elderly to better understand what they are being told in noisy environments.Although positive quantitative results in the SLSP do not necessarily reflect positive auditory performance in tested subjects, this test is an additional tool health care workers can use to obtain objective data to advise elderly patients fitted with hearing aids who still experience communication difficulties.Thus, it is possible to quantify and demonstrate to elderly subjects that it may take more than hearing aids for them to see significant improvements in communication skills.Guidance on communication strategies will possibly be better understood and internalized by patients and their families and generate interest and greater compliance to auditory rehabilitation programs when special attention is given to temporal auditory processing and the benefits it brings to one's communication ability.Hearing aids alone cannot address all patient auditory complaints. Good auditory performance is the outcome of a summation of factors involved in the hearing aid selection and fitting process, including auditory temporal processing.The findings of this study show that elderly subjects, regardless of peripheral hearing, performed better in speech recognition tests when sentences were played at a lower speech rate against a quiet background.As for speech in noise, the study suggested that elderly individuals with hearing loss had more significant improvements in speech recognition than subjects with normal hearing when sentences were presented at a lower speech rate.


ANSD is a challenging problem.To present our experience on management of the children with ANSD with respect to clinical data.This retrospective study included all children younger than 16 years of age who applied to the department between 2005 and 2013 . The data were derived from pure tone, OAEs and ABR tests, and further medical risk factors of the subjects were evaluated.ANSD was recognized in 74 ears of 40 children (B/U: 34/6) among 1952 children with SNHL (2.04%) detected among 9520 applicants to the department (0.42%). The clinical tests revealed that hearing loss greater than 15 dB was present in both ears of 38 cases. The degree of hearing loss was profound in 48% children, severe in 12% children, moderate in 28% children, mild in 10% children and normal in 5% children. ABRs were absent/abnormal in 37/3 ears and CMs were detected in all. Acoustic reflexes were absent in all ears. Rehabilitation was managed by CI and hearing aids in 15 and 23 cases, respectively. FM system was given to two cases displaying normal hearing but poor speech discrimination in noisy environments.ANSD is a relatively challenging problem for the audiology departments because of its various clinical features and difficulties in management. Our patients with ANSD most commonly displayed profound hearing loss. The number of overlooked cases may be minimized by performing ABR and OAE in every case referred with the suspicion of hearing loss. The hearing loss known as auditory neuropathy spectrum disorder (ANSD) has been described by the presence of otoacoustic emissions despite absent or severely abnormal auditory brainstem responses (ABRs).It has been reported that ANSD was related with various clinical and audiological patterns. Pure tone thresholds (PTAs) range from normal or near normal to severe hearing loss, particularly characterized by impaired auditory processing skills in noisy environments. These subjects present very low speech discrimination scores (SDS) which are not associated with the pure tone levels. Acoustic reflexes are absent in the majority of the cases.6It has been reported that, particularly because of poor SDS in relation to better PTAs, management process of children with ANSD is more problematic than that of children with other hearing loss patterns.11Our purpose in this study is to present our experience on the management of children with ANSD with respect to clinical data.This study has been done in a retrospective manner and included all children younger than 16 years of age, who applied to the audiology department between 2005 and 2013 . The subjects were first divided into two subgroups according to presence of sensorineural hearing loss (SNHL) (>15 dB),The audiological evaluation of patients who are suspected of having ANSD should include the following criteria: presence of CM; abnormal or absent ABR.The audiometric data of the subjects with ANSD and auditory perception skills – language development were evaluated.Age-specific pure tone audiometry from 250 to 6000 Hz was performed for all subjects using conversional, play or behavioral methods. Speech detection and recognition assessments included speech awareness test (SAT) for children and speech recognition threshold. Tympanometry and acoustic reflex evaluation were also performed at the time of testing. Acoustic reflex thresholds were measured ipsilateral and contralateral with pure tone stimuli from 500 to 4000 Hz. Stimulated ears were considered absent when there was no response to test intensities up to 110 dB HL.Click evoked otoacoustic emissions were measured with an ILO – 92 OAE system. The click level ranged from 80 to 86 dB peak sound pressure. Responses to as many as 260 stimuli were averaged over a 20 ms window and stored in two separate buffers. The presence of normal transient evoked otoacoustic emissions was determined by response amplitude of at least 3 dB and waveform reproducibility in at least three octave bands of >75%.ABR was recorded in a single electrode configuration, in a channel running from the forehead to the ipsilateral ear using a band-pass filter between 100 and 3000 Hz. Click stimuli consisted of one run of condensation followed by one run rarefaction clicks presented monaurally at rates of 13.0 per second and at intensities of 75 dB and, when necessary, at 95 dB HL. CM was demonstrated by the changing polarity in ABR. Patients underwent assessment in a sound treated room in a state of natural or chloral hydrate induced sleep.Auditory perception skills’ evaluation of children with hearing aids and cochlear implants was performed using the Ling sounds test, the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS), Meaningful Use of Speech Scale (MUSS) and LittlEARS.Ling sounds test is an auditory perception skills test and is used to evaluate both the detection and the discrimination of sounds. Six picture cards symbolizing the sounds were used to evaluate children during the test.The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) is a modification of the Meaningful Auditory Integration Scale (MAIS). It is a structured interview schedule designed to assess the child's spontaneous responses to sound in his/her everyday environment. The assessment is based upon information provided by the child's parent(s) in response to 10 probes. These 10 probes assess three main areas: (1) vocalization behavior, (2) alertness to sounds, and (3) deriving meaning from sound. Specific scoring criteria have been developed for each of the 10 probes.Meaningful Use of Speech Scale (MUSS) is a parent report scale, which is designed to assess the child's use of speech in everyday situations. It consists of ten inquiries which assess the following areas: vocal control, use of speech without gesture or sign and use of communication strategies in everyday situations.LittlEARS auditory questionnaire is a parent questionnaire designed to assess the auditory behavior of hearing impaired children who are provided with a CI or a hearing aid prior to their 24th month of life. It records preverbal auditory development during the first two years of hearing in the child's natural environment, taking into consideration reception, understanding and adequate response and vocal-verbal production of acoustic (linguistic) stimuli. The questionnaire consists of 35 age-related sorted questions to be answered with “yes” or “no” by parents.Direct assessment of expression and receptive language measures included the Preschool Language Scale, version 4 (PLS-4).SPSS 16.0  was used. Wilcoxon test was used to compare the auditory perception and language scores of the patients before and after hearing amplification.We found that 9520 children were evaluated in the department during the study period and sensorineural hearing loss was recognized in 1912 of them (20.08%). ANSD was found in 74 ears of 40 children . ANSD prevalence in the children population with sensorineural hearing loss was found to be 1.89%. The average age of children with ANSD at diagnosis was determined as 3.05 ± 2.44 years.As seen in All of the ears of the subjects had normal tympanogram and displayed no acoustic reflex response. As seen in Transient and distortion OAEs were detected in 32 ears although cochlear microphonics were present in all of the ears with AN. In six subjects with unilateral AN, the contralateral ears had severe-profound hearing loss without cochlear microphonics. In ABR, while only 8% of the patients presented abnormal wave morphology, the remaining ears had no wave-V. Presence of cochlear microphonics was changed by lateralization of ANSD ears.Two patients who had normal hearing were suggested to use the FM system for education. However, both parents of the patients did not wish their children to use them. Thus we did not follow up the FM system's effectiveness in ANSD with normal hearing .Figure 3Twenty-three of the patients were given hearing aids. Two of our patients with hearing aids had no sufficient benefit from its use, but they were not suggested implantation due to their age, irregular hearing aid use and insufficient rehabilitation. Fifteen of the patients with hearing aids did not come to follow-up and rehabilitation.Fifteen patients with ANSD were suggested cochlear implants and then they were operated on. Intraoperative impedancemetry and neural response telemetry (NRT) were within normal limits. None of them had immediate postoperative complications. Postoperative impedancemetry and neural response telemetry (NRT) were also within normal limits. However, four of the patients with hearing aids did not come to follow-up and rehabilitation.p < 0.05) (p < 0.05)  . For the < 0.05) .Figure 4p < 0.05) (p < 0.05) (p > 0.05).For the evaluation of auditory perception skills LING, IT MAIS, MUSS and LittlEARS scores were determined before the cochlear implantations and 12 months after the cochlear implant fittings depending on data availability. All patients with sufficient follow-up to date demonstrated significant improvement due to the hearing aids ( < 0.05) . For the < 0.05) . HoweverThe term auditory neuropathy was first used by Sininger and colleagues in 1995 and it is currently the most popular term used for the disorder. It should be understood as a consensus term used by researchers to describe the clinical condition of hearing loss characterized by absent ABRs with normal OAEs and CM.The patients who meet the criteria for the definition of auditory neuropathy represent a heterogeneous population as in our study. In fact, it is quite possible that not all patients with the clinical criteria for this disease have the same pathologic mechanism for their hearing disorder. It is likely that there are various reasons that account for the clinical findings of auditory neuropathy.1.Hearing loss, usually bilateral, of any degree2.Presence of OAEs and/or CM3.Abnormal or absent ABR4.Poor speech perception5.Absent acoustic reflexesThe audiological evaluation of patients who are suspected of having auditory neuropathy must be comprehensive. It should include the following criteria:The diagnostic hallmark of ANSD is the combination of other normal hair cell activity and abnormal afferent and efferent auditory neural functions probably at the level of the eighth cranial nerve and brainstem. Outer hair cell activation is assessed indirectly by the acoustic energy emitted by the inner ear (OAEs) and the electrical response from the cochlea (CM).In cochlear hearing loss OAEs and CM are absent and, subsequently, the ABR threshold is elevated. However, in ANSD, the ABRs are abnormal or absent, whereas the OAEs and/or CM are normal. Cases of absent ABRs in the presence of mild to moderate hearing loss were reported in some series.It was reported that the majority of patients with ANSD have absent acoustic reflex, with about 20% having highly atypically (elevated) acoustic reflex both ipsilaterally and contralaterally, but have recordable acoustic reflex to tactile stimulation.The hearing loss in ANSD may range from mild to profound and audiograms vary widely; no predominant pattern has been detected.Given such an incipient understanding of ANSD, amplification and auditory rehabilitation for these patients is challenging. For pediatric patients a comprehensive, multidisciplinary approach to the management of ANSD is recommended. A trial of hearing aid amplification should be performed depending on the audiological information. FM system can also be tried. FM systems are recommended in both ANSD patients with normal hearing and hearing aid and cochlear implant users because of the improved speech understanding in noisy conditions. Therefore, it is believed to increase success in education. In addition, at the time the cochlear implant team should evaluate the patient and then determine the candidacy for cochlear implantation based on the audiological findings, hearing aid benefit, status of speech language development and overall development skills.Auditory rehabilitation with hearing aids is difficult for patients with ANSD because of the poor word recognition.Cochlear implant provides supraphysiologic electrical stimulation to the auditory nerve and may improve the synchronicity of the neural activity.Comprehensive audiological evaluation is required for accurate diagnosis. The best management of ANSD is provided by a multidisciplinary approach, and amplification preferences should be chosen depending on the hearing loss degree and language development as SNHL.Çağıl Gökdoğan was in charge of data collection, analysis and the writing of the paper; Şenay Altınyay was in charge of data collection, analysis and the writing of the paper; Bülent Gündüz was in charge of data collection, analysis and the writing of the paper; Yusuf Kemal Kemaloğlu was in charge of the writing of the paper; Yıldırım Bayazıt was in charge of the writing of the paper, and Kemal Uygur was in charge of the writing of the paper.The authors declare no conflicts of interest.


Sudden sensorineural hearing loss is relatively frequent. In most cases, the etiology is not discovered. One of the possible causes for sudden deafness is inner labyrinth bleeding, which was difficult to diagnose before the advent of magnetic resonance imaging. The purpose of this paper is to report a case of sudden hearing loss caused by a labyrinthine hemorrhage, and to present a review of the literature on this topic. Sudden sensorineural hearing loss (SSHL) is generally unilateral, sudden, or rapidly progressive hearing loss,The aim of this paper was to report a case of SSHL probably caused by intralabyrinthine hemorrhage, in a Marfan’s syndrome patient that was under anticoagulation therapy. A review of the literature is also presented.E.F.G, a male patient aged 40 years, sought our unit and complained of sudden right-ear hearing loss that had started five days previously. There was not tinnitus, vertigo or aural fullness. Marfan’s syndrome had been diagnosed in this patient; he had undergone aortic valve heart surgery three years ago . The patient had been prescribed a betablocker and regular oral anticoagulation medication.The physical examination showed acromegaly; the heart auscultation evidenced the metal aortic prosthesis. The static and the dynamic balance were normal; there was no spontaneous or semi-spontaneous nystagmus. Pure tone audiometry revealed profound sensorineural hearing loss in the right ear . CoagulaThe patient was treated medically, resulting in improvement of hearing (20 dB) and decreased vertigo.SSHL is defined as sensorineural audiometric loss of 30dB or more at three consecutive auditory frequencies, arising within not more than 72 hours.Causes of SSHL may be infectious , vascular, immunomediated , or resulting from neurological disease , neoplasms or ototoxicity.Four theories based on histopathology have been developed to explain the pathophysiology of SSHL: a viral infection, an immunological origin, membrane rupture, and circulation disorders.The vascular etiology of SSHL may be hemorrhagic or obstructive. Intralabyrinthine hemorrhage (ILH) is a rare complication in patients that have hematological disease and/or under anti-coagulation therapy,De Klein postulated that central vascular injury could be the cause of auditory disorders;ILH has been described in patients with aplastic anemia,T1-weighted MRI is valuable in the diagnosis of ILH. In normal subjects, the perilymph and the endolymph are isointense compared to the cerebrospinal fluid; the presence of fat, decreased blood flow, high protein concentration, or metahemoglobin14Until the current date, no study had been published attributing the cause of ILH to degeneration caused by Marfan’s syndrome.The treatment of SSHL remains extremely controversial even when the etiology is found. Clinical improvement attributed to hyperbaric oxygen therapy, anti-hypertensive drugs, anticoagulants, corticosteroids, plasma expanders, and hygienic-dietetic measures have not been shown to be superior to spontaneous cure.15The abrupt onset of hearing loss associated with vertigo and the presence of a hypersignal in fat-suppressed T1-weighted MRI images of labyrinthic fluid strongly suggests acute intralabyrinthine hemorrhage. This minor hemorrhage may be the first complication of anticoagulation therapy.In our patient, evidence suggests that sudden sensorineural hearing loss resulted from hemorrhage due to oral anticoagulation therapy, rather than possible morpho-physiological alterations typical of Marfan’s syndrome.