Hearing loss is a global public health problem putting millions of people at risk of experiencing impediments in communication and potentially impaired mental health. Many studies in this field are based on small, cross sectional samples using self-report measures. The present study aims to investigate the association between childhood sensorineural hearing loss and mental health in adult men and women longitudinally in a large cohort with a matched control group, and hearing is measured by pure-tone audiometry. Studies of this kind are virtually non-existing.N = 66), 26–40 dB as mild (N = 66) and 16–25 dB as slight (N = 220). Mental health in adulthood was measured in HUNT 2 by symptoms of anxiety and depression, subjective well-being, and self-esteem. The association between childhood sensorineural hearing loss and adult mental health was tested by means of ANOVA.The present study combines data from two large studies; the School Hearing Investigation in Nord-Trøndelag (SHINT) carried out yearly from 1954 to 1986, and the second wave of the Nord-Trøndelag Health Study (HUNT 2) conducted from 1995 to 1997. The participants were 7, 10 or 13 years during the SHINT, and between 20 and 56 years old during HUNT 2. The total sample consisted of 32,456 participants . Participants with a sensorineural hearing loss in SHINT of 41 dB or more were classified with moderate-severe hearing loss (p = 0.038). Further investigation of the results revealed a significant association between slight hearing loss and symptoms of anxiety and depression  and between mild hearing loss and lowered self-esteem  among women aged 20–39 years. There were no significant relations between childhood sensorineural hearing loss and any of the three mental health outcomes among men.There was a significant relation between slight childhood sensorineural hearing loss and lowered subjective well-being in women (B = −.25, This study suggests that women with slight or mild sensorineural hearing loss from childhood experience elevated levels of symptoms of anxiety and depression, lowered subjective well-being and lowered self-esteem. However, the results should be interpreted with caution due to a lack of power in some analyses. Hearing loss is a global public health problem, listed by the World Health Organization as one of the leading causes of disability worldwide . An estiOne of the most important repercussions of any hearing loss is the impediment of communication . The inaA number of studies have demonstrated an association between hearing loss and mental health in children and adolescents. Recently, Theunissen and colleagues  reviewedAlthough there seems to be a growing body of research demonstrating a relationship between hearing loss and mental health and self-esteem, results are not unanimous. Mejstad and colleagues  invited Finally, Øhre and colleagues  examinedTo sum up, there is broad agreement among researchers that hearing loss is a public health problem that may have detrimental effects, that it is a complex and understudied issue, and that more research is needed –20. DespThe aim of the present study is to investigate the relation between childhood sensorineural hearing loss and mental health in adult men and women, respectively, in terms of subjective well-being, self-esteem, and symptoms of anxiety and depression. In a previous paper based on cross-sectional data, we found a weak to moderate association between hearing loss and mental health in adults , and nowThe present study combines baseline data from the School Hearing Investigation in Nord-Trøndelag (SHINT) with follow-up data from the Nord-Trøndelag Hearing Loss Study (NTHLS) and the second wave of the Nord-Trøndelag Health Study (HUNT 2) in Norway. All NTHLS participants also participated in the HUNT 2. Altogether, data from three questionnaires are used in this study: the questionnaire from the NTHLS (NTHLS-Q1), and both questionnaires from HUNT 2 (HUNT2-Q1 and HUNT2-Q2). The HUNT2-Q2 was handed out at the examination cite and returned by mail later, the response rate for the sample used in the present study was 76.3%.The SHINT was an audiometric screening of all schoolchildren attending regular schools in the county of Nord-Trøndelag aged 7, 10 and 13 years from 1954 to 1986. The late H.F. Fabritius who was a Norwegian Ear, Nose and Throat (ENT) specialist, led the investigation. Great efforts were made to ensure participation, and Dr. Fabritius himself even rowed a boat to reach a small island off the Norwegian coast in order to include the people who lived there. Unfortunately, the exact number of participants is unknown, since records were only made for children with hearing loss, and not for children with normal hearing. We do know, however, that 78,524 children were born in Nord-Trøndelag between 1941 and 1977, which may serve as a proxy.The initial screening included as good as every single pupil in the entire county and took place in a quiet location at the respective school. A trained hearing assistant or a nurse performed the hearing examination. Air-conduction thresholds were obtained by means of pure tone audiometry at 0.25, 0.5, 1, 2, 4 and 8 kHz utilizing Amplivox audiometers . Pupils were registered with hearing loss if 1) thresholds of 20 dB or greater at three or more frequencies in the same ear were detected, or if 2) a threshold of 30 dB or more at one or more frequencies were detected.A total of 10,269 children were classified with hearing loss at the screening. All of these children were then invited to a full examination by an ENT specialist at one of the 14 out-patient clinics in Nord-Trøndelag. Questionnaire data regarding the children’s ear problems were collected from the parents. The ENT specialist performed a new pure tone audiometry with both air- and bone-conduction thresholds as well as a complete medical examination including family and medical history, recording findings and diagnoses. Children underwent one or more ENT examinations depending on the diagnoses in order to ensure correct classification. Dr. Fabritius defined SNHL as hearing loss in which the air-conduction thresholds followed those of the bone-conduction, although he did not include a maximum accepted air-bone gap in this definition. In this study, we rely on the diagnosis made by Dr. Fabritius and the other ENT specialists. The attendance rate was 97% between 1954 and 1962 and it is likely that the high participation rate persisted .Out of the 10,269 children who tested positively for hearing loss at the screening, 1489 were diagnosed with Sensorineural Hearing Loss according to Dr. Fabritius’ definition. However, only 3066 out of the 10,269 children from the screening in the SHINT also participated in the NTHLS as adults, and just 462 out of the original 1489 SNHL cases from the SHINT also participated in the NTHLS. There were several reasons for this attrition, like for example loss of identification number or not being old enough to be invited to the NTHLS, or possibly moving away from the county .For the purpose of the present study, we wanted to distinguish between profound-severe, moderate, and mild hearing loss, respectively. We estimated the average hearing threshold of 0.5, 1, 2 and 4 kHz in both ears from the last audiogram , which for most participants was at age 13. This means that the hearing loss might have emerged at different points in time for the participants, somewhere between birth and 13 years of age. We defined moderate-severe hearing loss as 41 dB or more , mild hearing loss as 26–40 dB, and slight hearing loss as 16–25 dB, resulting in 67 cases in each of the two former groups and 223 cases in the latter. This reduced the case group from 462 to 357.Finally, since the present study has mental health variables as outcome, we wanted to exclude cases that might be struggling with mental health problems at baseline. We cross-checked the case group with data on the following conditions registered at baseline: “Retarded”, “Cerebral paralysis”, “Mental health issues”, “Mental distress/ depressed”, “Down’s syndrome”, and “Is receiving psychological treatment”. Three individuals were registered as “Retarded”, one individual was registered with “Cerebral paralysis”, and one individual with “Downs syndrome”. These cases were excluded from further analysis, resulting in a total case group of 357 of which 220 are in the case group with slight hearing loss whereas the other two groups include 66 individuals each.The NTHLS was a part of the second wave of the Nord-Trøndelag Health Study (HUNT 2) carried out in 1995–97. In HUNT 2, the entire adult population in Nord-Trøndelag County was invited to participate, whereas in NTHLS, the adult population in 17 of the 23 municipalities was invited to participate. Data on mental health were available for 51,574 people (62.8%) and the age span was 20 to 101 years. Participants in the NTHLS who had not been diagnosed with a hearing loss at SHINT were used as the reference group, following the assumption that all of these people grew up in Nord-Trøndelag and therefore participated in the SHINT. Since the SHINT lasted from 1954 to 1986 and the NTHLS from 1995 to 1997, the oldest participants to attend both SHINT and NTHLS would have been 13 years in 1954, thus 56 years old in 1997. Therefore, we only selected people 56 years and younger from the NTHLS for the reference group. This resulted in a sample of 32,456 individuals.To sum up, the sample consisted of 66 individuals with moderate-severe hearing loss, 66 with mild hearing loss, 220 with slight hearing loss, and 32,104 with normal hearing (reference group).For the purpose of the present study, only children diagnosed with SNHL were selected. In the present study, we estimated the average hearing threshold of 0.5, 1, 2 and 4 kHz in both ears from the last audiogram. We defined moderate-severe hearing loss as 41 dB or more, mild hearing loss as 26–40 dB, and slight hearing loss as 16–25 dB.Ten of the 25 items from the Symptom Checklist-25 , here caThe index consists of three items from HUNT2-Q1, phrased as follows: When you think about your life at the moment, would you say that you are by and large satisfied with life, or are you mostly dissatisfied? (seven response categories ranging from “very happy” to “very unhappy”); In the course of the last 2 weeks, have you been feeling safe and calm?; In the course of the last 2 weeks, have you been feeling happy and optimistic? (four response categories ranging from “no” to “a lot” for both items). The first question was recoded so that a high score on this variable reflects a high level of subjective well-being. Because of the different number of response categories, the items were standardized before they were added into a sum score indicator. Cronbach’s alpha was .84.Four items from The Rosenberg Self-Esteem Scale  were incThe scores for all of the three outcome variables were standardized before entered in the analyses.Control variables included in this study are age, education, mother’s education and father’s education, respectively. The data were provided by Statistics Norway with the following ten categories: 1) No education/preschool, 2) primary school 1st to 7th grade, 3) middle school 8th to 10th grade, 4) high school 11th to 12th grade, 5) high school diploma 13th grade, 6) high school extended, 7) college or university, lower level, 14th to 17th grade, 8) college or university, higher level, 18th to 19th grade, 9) PhD level, 20th grade or more, 10) education not reported. We recoded categories 1, 2, 3 and 10 into “Primary school”, category 4 into “middle school”, categories 5 and 6 into “high school”, category 7 into “college/university, less than 4 years”, and categories 8 and 9 into “college/university, 4 years or more”.N = 10,269).As mentioned earlier, records for normal hearing were not registered in the SHINT, which means that for many frequencies, values below 20 dB were missing. The missing value for each frequency was therefore replaced by the frequency specific mean values of the scores below 20 dB in the original sample , expectation maximization (EM) for imputation of missing data where the respondent had valid data on at least half of the items. The ten SCL items were used to predict each other. This reduced missing values from 7.9 to 0.3%. For SWB, the items were used to predict each other in those cases where the respondent had valid data on two of the three questions, reducing missing values from 8.0 to 4.9%. The Self-esteem items were included in HUNT2-Q2, and, as mentioned above, this questionnaire was returned by somewhat fewer respondents (76.3%) than the other two questionnaires. For this reason, there was a larger percentage of missing values on the Self-esteem variable compared to the SCL-10 and SWB variables. Missing data were replaced for respondents who had valid data on at least two of the four items. The four Self-esteem items were used to predict each other, reducing missing values from 19.6 to 17.8%.A total of 319 participants (0.9%) as well as 4697 fathers (14.5%) and 3402 mothers (14.5%) did not report level of education and missing values were replaced by the sample mean.This study applies a longitudinal design, investigating the association between childhood sensorineural hearing loss at baseline and adult mental health up to 43 years later. In order to study this association separately in men and women, we split the dataset into to new datasets; one including men only, and one with women only. Three ANOVA analyses  were conducted consecutively in each data set  with Childhood Sensorineural Hearing Loss (CSNHL) as the predictor and SCL-10, Subjective Well-Being, and Self-Esteem as the respective outcomes. Since the dependent variables were standardized before entered in the analyses, the unstandardized regression coefficients (b) show adjusted group mean differences scaled in fractions of a standard deviation. This makes it easier to interpret the results. The first model tests the association between childhood sensorineural hearing loss and adult mental health, whereas the second model tests the same association controlled for age, education, and mother’s and father’s education, respectively. In the analyses with the total sample we also included sex as a control variable .Descriptive statistics for the three case groups with childhood sensorineural hearing loss  and for the reference group without childhood sensorineural hearing loss, respectively, are presented in Table The unadjusted and adjusted results from the ANOVA analyses are presented in Tables Table p = 0.161, and B = .22, p = 0.083, respectively).Table p = 0.054) as well as a significant association between mild hearing loss and lowered self-esteem  among women in the youngest age group. Although the associations between slight hearing loss and self-esteem among women in the youngest age group and between slight hearing loss and lowered subjective well-being among women in the oldest age group had small to moderate effect sizes, they did not reach significance .We took the analysis one step further by dividing the sample of women into two different age cohorts; one aged 20–39 years and one aged 40–56 years. Rerunning the analyses in each age cohort revealed a significant association between slight hearing loss and symptoms of anxiety and depression . How. How15])It is difficult to explain why we did not detect any effects among the men with hearing loss in our study. It is possible that this reflects a gender difference in which women with hearing loss struggle more when they enter adulthood. Perhaps women find the impediments that the hearing loss puts on communication more burdensome than men, or perhaps this merely reflects the tendency for women in general to score higher on anxiety and depression than men .The size of the SHINT  and NTHLS/HUNT  investigations and the possibility to follow the children with hearing loss all the way into adulthood more than 40 years later makes our data material rather unique. No other study has been able to do this, as far as we know. Since children were screened for hearing loss at three different ages , most cases have probably been identified. Another strength is the use of pure tone audiometry, which leaves little room for measurement error. Obviously, hearing measurement equipment did not hold the same standard in the 1950’s as in the 1980’s, however, the researchers used the best equipment following international standards at the time. What is more, the children were thoroughly examined one or more times by an ENT specialist using air- and bone conduction thresholds. Hence, we feel reasonably sure that most cases were indeed identified. However, although all efforts were made to ensure correct identification of sensorineural hearing loss, the occurrence of misclassification cannot be completely ruled out. Also, we do not know if the children received hearing aids of any kind.The recording of additional disorders and problems in the SHINT allowed us to exclude individuals who had been registered with mental health problems at baseline from our study. This means that we can be reasonably sure that the children included in our study were relatively mentally healthy at baseline. We know that the researchers who collected the data in the SHINT were meticulous in their work. Furthermore, it is not very likely that the children in our study struggled with many severe challenges other than the hearing loss, since children with multiple challenges are normally referred to special schools.Although it is an advantage to be able to follow up a cohort over more than forty years, it is also a challenge. Firstly, many things may have happened in between baseline and follow-up; people may get a mental illness and still have plenty of time to recover without us knowing. Even if our failing to detect a relation between hearing loss and mental health among men reflects a true absence of associations, our results do not necessarily mean that boys with hearing loss automatically learned to cope with their hearing loss and then uninhibitedly reached adulthood with their mental health intact. We cannot know for sure. Secondly, it might have been very different growing up with sensorineural hearing loss in the 1950’s than in the 1980’s. There is a larger acceptance and understanding for minority groups of all kinds now that hopefully makes it somewhat easier for people with hearing loss to navigate in the hearing world. But following such a line of reasoning, one might have expected more mental health problems among the eldest group of adults and not the youngest, but that was not the case. Rather, if it is the youngest adults that struggle the most, then this is especially important to address in our (seemingly) accepting society. On the other hand, maybe the eldest group struggles just as much, only we did not have the statistical power to detect it.There was a loss of observations from the SHINT to the NTHLS, as only 3066 of the 10,269 original cases participated in the NTHLS. Our research group investigated this in a previous article  and founOur reference group consisted of adults who participated in the NTHLS and who were not registered with hearing loss at the SHINT. This means that we assume that these people went to primary school in Nord-Trøndelag and, consequently, that they attended SHINT. This is a rather crude approximation. The reference group undoubtedly includes some false negatives since some of the respondents in this group may have moved to Nord-Trøndelag as young adults, and therefore did not attend the SHINT. However, this would not have affected our results much since even a substantial number of false negatives in the reference group would have been greatly outnumbered by the true negatives.Our study suggests that girls with slight or mild SNHL are at risk of having mental health problems as adults. On the one hand, this supports earlier research showing an association between hearing loss and mental health in general, but on the other hand, it contradicts it, since we only detected effects for women and not for men. Studies on hearing loss are vulnerable to attrition and our study is no exception; our results therefore need to be interpreted with caution. This field of research is still in great need of more longitudinal studies based on large, representative samples in order to disentangle the many complex issues related to hearing loss and mental health.


To evaluate indications, results and strategy of retinal exams requested at Primary Care Units.diabetes mellitus and/or hypertension, in use of drugs with potential retinal toxicity, diagnosis or suspicion of glaucoma, stable and asymptomatic retinopathies, except myopia greater than -3.00 diopters. A retrospective study that analyzed the indications and results of retinal exams, in the modalities clinical dilated fundus exams and color fundus photographs. In the following situations, patients were considered eligible for color fundus photographs if visual acuity was normal and ocular symptoms were absent:  A total of 1,729 patients were evaluated , and 1,190 underwent clinical dilated fundus exam and 539 underwent color fundus photographs. Diabetes was present in 32.2%. The main indications were diabetes (23.7%) and glaucoma evaluation (23.5%). In 3.4% of patients there was no apparent indication. The main results were a large cup/disc ratio (30.7%) and diabetic retinopathy (13.2%). Exam was normal in 9.6%, detected peripheral changes in 7% and could not be performed in 1%. Considering patients eligible for fundus photographs (22.4%), more than half underwent clinical dilated fundus exams. Regarding exam modality, there were no important differences in the distribution of indications or diagnosis. Color fundus photograph is compatible with telemedicine and more cost-effective, and could be considered the strategy of choice in some scenarios. Since there are no clear guidelines for retinal exams indications or the modality of choice, this study may contribute to such standardization, in order to optimize public health resources. Retinal diseases are the most common causes of blindness in adults of urban populations in Brazil. 7 besides allowing expanded access to diagnosis when there is an imbalance between offer and demand for specialists.9 Currently, in the Brazilian public health system, there are no precise guidelines as to the type of retinal examination that should be requested.The primary methods to evaluate the retina are clinical dilated fundus exam (DFE), performed by a specialist and digital photography of the retina, called color fundus photographs (CFP), which can be obtained by a non-medical professional and later interpreted by a specialist. Both modes are effective for detecting modifications in the retina and optic nerve, and CFP can be integrated to telemedicine protocols, a combination that offers a good cost-effective profile,To evaluate the indications, results, and strategy of retinal examinations requested for patients of the Primary Care Units.Centro Diagnóstico de Oftalmologia ) of the Instituto Israelita de Responsabilidade Social Albert Einstein (IIRS). Tests performed within the period of approximately 10 years, between October 31, 2007 and June 5, 2017, were analyzed.This is a retrospective study, based on the analysis of medical records of patients examined at the Ophthalmology Diagnosis Center , who worked at Primary Care Units, situated in peripheral zones of the city of São Paulo (SP). The care delivered at the Primary Care Units and the performance of tests at the CDOF were part of the partnership established between the IIRS and the City Administration of São Paulo.All tests were requested by the same medical staff composed of 21 ophthalmologists of Dilated fundus exam was conducted by two ophthalmologists specialized in retinal diseases, with indirect binocular ophthalmoscopy complemented by biomicroscopic fundoscopy with a slit lamp.Called CFP assessments were performed by ophthalmic technicians on Zeiss FF 450 equipment , with an angle of 50°, and documentation of the posterior pole and periphery. Such images were interpreted by the same two physicians specialized in retinal diseases.The following clinical and demographic data were analyzed: sex, age, corrected visual acuity, presence of diabetes (self-reported), main indication of the retinal examination, and results of this test. Indication of the test was based on the ocular and/or systemic history, complaint and on visual acuity; in cases in which there was more than one complaint or medical condition, we considered the condition that posed more risk to vision. For patients who underwent more than one examination during that period, information was collected as to the first examination performed in the period.diabetes mellitus ; diagnosis or suspicion of POAG; hypertension; history of ocular trauma; personal or family ophthalmologic history; and complaint or clinical picture consistent with another ocular disease that possibly affects the posterior segment (not mentioned in the categories above). Also categorized were the patients who did not present with any evident indication of retinal examination  and those for whom there were no data appropriately filled in on the medical record.For analysis of the indication of the retinal examination, the following clinical conditions were categorized   : late pThe study was approved by the Ethics Committee of the organization, under no. 2.338.968. CAAE: 77215417.0.0000.0071.diabetes mellitus ; hypertensive; patients on oral medication with potential retinal toxicity; with diagnosis or suspicion of POAG; and with stable and asymptomatic retinopathies, except for myopia greater than -3.00 diopters. For analysis of indication of the study strategy, the following situations were considered eligible for evaluation by CFP, in cases of good visual acuity  As to analysis of the examination result, the evaluation took into consideration both eyes of each patient; when there was more than one diagnosis, the primary retinal modification was considered − the one that poses more risk to vision. Besides the primary diagnosis, the presence of DR and of the increase in cup/disc ratio was individually assessed.t test was used, and the χ2 test was employed to compare the categorical variables. The p value <0.05 was considered statistically significant.For the statistical analysis, the IBM Statistical Package for the Social Sciences (SPSS) for Windows, version 20  software was used. The continuous variables are described as mean and standard deviation, and the categorical variables, as absolute and relative frequencies. To compare continuous variables, the non-paired Student’s A total of 1,729 patients were evaluated; of these, 1,190 underwent DFE and 539, CFP. Of the 1,729 patients, 10  in whom it was not possible to evaluate the indication of the examination, were excluded. Fifty-eight (3.4%) patients had no apparent indication for the retinal exams as per the criteria numbered above; 42 patients were submitted to DFE and 16 to CFP. As to the modality of examination, 386 patients (22.4%) presented with an indication for retinal examination and were eligible for the CFP modality. Of all patients eligible for CFP, 229 (59.3%) were submitted to DFE, which corresponded to 13.3% of the overall total. The reasons for requesting examinations in this group of patients were follow-up of stable retinopathy  in 16 patients (6.9%); use of oral medication with potential retinal toxicity in 8 patients (3.5%); diagnosis of diabetes in 83 patients (36.2%); diagnosis or investigation of POAG in 86 patients (37.5%); diagnosis of hypertension in 36 patients (15.7%).The primary diagnoses found in the retinal examinations are shown on In the present study, the primary indications for performing the retinal examination for patients evaluated in a Primary Healthcare Unit were diabetes (23.7%) and investigation of glaucoma (23.5%); in diabetic individuals, the exam was normal in 34.3% of cases. The main diagnoses were large cup/disc ratio (23.2%) and DR (12.8%); in patients with a normal result, the main indication for the examination was the presence of diabetes (34.3%). It was considered that in only 3.4% of cases, the test was requested with no apparent indication. The DFE was the most frequently performed examination (68.8%); nevertheless, considering all patients eligible for use of the CFP modality, approximately 60% of these were submitted to DFE.13 As examples, we can cite the detection of choroid nevus as an exam finding and its low risk of malignant transformation, Currently, there is no consensus as to the need for performing the retinal examination under mydriasis in individuals not presenting with signs or symptoms of diseases of the posterior ocular segment, or who have no risk factors for the development of such diseases, since conditions detected in routine examinations under pupil dilation and that generate changes in management or prevention of an outcome are rare.Conselho Brasileiro de Oftalmologia (CBO) [Brazilian Ophthalmology Council] drew up a protocol recommending the performance of DFE in the following situations: preoperative period of cataract surgery or of refractive surgery; acute or chronic entoptic phenomena; high myopia; family or personal history of retinal detachment, ocular trauma and hypoxic retinopathies . The American Academy of Ophthalmology (AAO) recommends that a complete ophthalmologic examination be done in 40-year-old individuals, but does not specifically mention pupil dilation. 19 or in patients with symptoms of posterior vitreous detachment is a clear indication of DFE, which allows evaluation of the extreme periphery of the retina, contrary to the conventional CFP. In clinical practice, however, tests for retinal examination are requested as part of the complementary ophthalmologic or clinical investigation in several other ocular or systemic conditions that potentially affect the posterior segment of the eye. Considering the two main strategies of retinal examination, DFE and CFP, there seems to be no clear indications as to the situations in which one or the other is most indicated; the choice should take into consideration some factors, such as availability of the exam, cost-effectiveness, and the specific clinical condition. For example, the investigation of predisposing lesions for retinal detachment in patients with myopiaIn most indications for the exam, there was no significant difference between the request of one or the other diagnostic modality, with the following exceptions: myopia greater than -3.00 diopters, investigation of low visual acuity and arterial hypertension, in which there was a significant predominance of DFE indication; and the investigation of glaucoma, in which the indication of CFP predominated. There were also no important differences in the distributions of diagnoses obtained by each modality.20 since it is compatible with telemedicine and does not require the presence of the specialist at the time of the examination. It has a high initial cost for equipment acquisition and structure assembly, which tends to be diluted posteriorly. In the situation studied here, the service already had the equipment, which conferred to this series a better cost-effective profile for the CFP strategy. Some studies carried out in Brazil have evaluated the adequacy of CFP associated with telemedicine for demand relief,21 especially in tracking DR within a scenario of a global epidemic of diabetes. Generally, both diagnostic methods for retinal evaluation studied show equivalent results and are strategically interchangeable, with some situations in which CFP can be considered the method of choice due to the cost-effectiveness profile,.Additionally, evaluation by digital CFP enables interaction with artificial intelligence algorithms to help in tracking and in clinical decision-making, which shows a tendency for the future. Conselho Federal de Medicina [Federal Medicine Council] published in February 2019, and revoked on February 22 (resolution 2.227/2018). During the preparation of this article, Brazil was in the middle of a controversial situation regarding standardization of telemedicine, based on the resolution of the Among the strengths of this study, we can highlight the large number of patients examined at the same center, over a long period of approximately 10 years, and the evaluation of one of the scenarios that corresponds to the reality of our country. The presentation of these data may help in the planning of protocols with the objective of a better use of resources. Among the limitations of the study, we mention the possible biased choice of examination due to agenda restrictions, besides patients who had the exam requested and did not actually undergo the exam. Another bias focuses on the photographic documentation of patients with diagnosis or suspicion of glaucoma, since they had the availability of a special type of CFP, the stereoscopic photography of the papilla, which documents the optic nerve with greater magnification. Many patients of this category may have been submitted to this modality, and therefore the diagnosis of glaucoma or suspected glaucoma in the sample studied was underestimated. Even so, diagnosis or suspicion of glaucoma were two of the main indications for the examinations, and large cup/disc ratio was the primary diagnosis found. Finally, there are cases of patients who had both types of exam modalities requested, but only the first exam to be done was considered for the analysis of indications and results, adding one more bias in our results and conclusions.The data assessed in this study point to the fact that the primary indications for requests of the retinal exam were diabetes and the investigation of glaucoma, and the main results of the exams were large cup/disc ratio and diabetic retinopathy. In the absence of well-defined guidelines for the request of exams for retinal evaluation, and with no criteria for the choice of modality of the retinal exam, data revealed that, in daily clinical practice, the exam modality is generally chosen in an interchangeable manner. Considering that the different strategies studied have distinct profiles of cost-effectiveness, it is suggested to establish guidelines for indications of retinal examinations and the standardization of the modality most indicated in each situation, to optimize resources of the public healthcare system. 1 A retinopatia diabética (RD) é a principal causa de cegueira na população economicamente ativa nos países desenvolvidos.2 O rastreamento da RD, assim como o exame periódico da retina em portadores de diabetes, faz parte das recomendações internacionais para os cuidados oculares em diabetes.3 Além da RD, em nosso meio, a degeneração macular relacionada à idade (DMRI) e o descolamento de retina são importantes causas retinianas de cegueira.1 O glaucoma primário de ângulo aberto (GPAA) é uma doença que pode levar a danos no nervo óptico, estrutura que também é avaliada durante exame do segmento posterior ocular.Exames de retina podem ser solicitados em diversas situações clínicas, como na investigação de baixa acuidade visual, ou de condições oculares ou sistêmicas com potencial de acometimento da retina ou do nervo óptico. Doenças da retina são a causa mais comum de cegueira em adultos em populações urbanas no Brasil.7 além de permitir ampliação do acesso ao diagnóstico, quando há desequilíbrio entre a oferta e a demanda de especialistas.9 Atualmente, no sistema público de saúde brasileiro, não há diretrizes precisas em relação ao tipo de exame de retina que deve ser solicitado.Os principais modos de se avaliar a retina são: o exame de mapeamento de retina (MR), realizado por especialista, e a fotografia digital da retina, denominada retinografia (RET), que pode ser obtida por profissional não médico e, posteriormente, interpretada pelo especialista. Ambos os modos são eficazes para a detecção de alterações da retina e do nervo óptico, sendo que a RET pode ser integrada a protocolos de telemedicina, combinação que apresenta bom perfil de custo-efetividade,Avaliar as indicações, os resultados e a estratégia de exame da retina solicitados para pacientes de Unidades Básicas de Saúde.Trata-se de estudo retrospectivo, realizado a partir da análise de prontuários de pacientes examinados no Centro Diagnóstico de Oftalmologia (CDOF) do Instituto Israelita de Responsabilidade Social Albert Einstein (IIRS). Foram analisados exames realizados no período de aproximadamente 10 anos, compreendidos entre 31 de outubro de 2007 e 5 de junho de 2017.Todos os exames foram solicitados por um mesmo corpo clínico composto por 21 médicos oftalmologistas do Hospital Israelita Albert Einstein (HIAE), que atuavam em Unidades Básicas de Saúde, situadas em zonas periféricas da cidade de São Paulo (SP). O atendimento nas Unidades Básicas de Saúde e a realização de exames no CDOF faziam parte de parceria estabelecida entre o IIRS e a Prefeitura Municipal de São Paulo.Os MR foram realizados por dois oftalmologistas especializados em doenças da retina, com oftalmoscopia binocular indireta complementada por biomicroscopia de fundo em lâmpada de fenda.As RET foram realizadas por tecnólogos oftálmicos em equipamento Zeiss FF 450 , com ângulo de 50°, e documentação de polo posterior e periferia. Tais imagens foram interpretadas pelos mesmos dois médicos especializados em doenças da retina.Foram avaliados os seguintes dados clínicos e demográficos: sexo, idade, acuidade visual corrigida, presença de diabetes (autorreferida), principal indicação do exame de retina e resultados do exame de retina. A indicação do exame baseou-se no histórico ocular e/ou sistêmico, na queixa e na acuidade visual; nos casos em que existia mais de uma queixa ou condição clínica, foi considerada aquela que mais trazia risco à visão. Para pacientes que realizaram mais de um exame no período, foram colhidas as informações referentes ao primeiro exame realizado no período.diabetes mellitus ; diagnóstico ou suspeita de GPAA; hipertensão arterial sistêmica; antecedente de trauma ocular; antecedente oftalmológico pessoal ou familiar; e queixa ou quadro clínico compatíveis com outra doença ocular com possível acometimento do segmento posterior (não citada nas categorias acima). Também foram categorizados os pacientes que não apresentavam indicação evidente do exame da retina  e aqueles para os quais não existiam dados adequadamente preenchidos em prontuário.Para a análise da indicação do exame de retina, as seguintes situações clínicas foram categorizadas   : pós-opO estudo foi aprovado pelo Comitê de Ética da instituição, sob o número 2.338.968, CAAE: 77215417. 0.0000.0071.10 e na ausência de sintomas (rastreamento): pacientes portadores de diabetes mellitus ; portadores de hipertensão arterial sistêmica; em uso de medicação oral com potencial toxicidade retiniana; com diagnóstico ou suspeita de GPAA; e com retinopatias estáveis e assintomáticas, exceto miopia maior que -3,00 dioptrias.11 Tais critérios não fazem parte de consenso e foram propostos para a realização deste estudo.Para análise da indicação da estratégia do exame, considerou-se que as seguintes situações eram elegíveis para avaliação por RET, em casos de boa acuidade visual Em relação à análise do resultado do exame, a avaliação levou em conta ambos os olhos de cada paciente; quando havia mais de um diagnóstico, considerou-se a principal alteração retiniana − aquela que trazia maior risco à visão. Além do diagnóstico principal, avaliou-se também individualmente a presença de RD e do aumento da escavação papilar.Statistical Package for the Social Sciences (SPSS), para Windows, versão 20 . As variáveis contínuas estão descritas na forma de média e desvio padrão, e as variáveis categóricas, de frequências absolutas e relativas. Para comparar variáveis contínuas, foi utilizado o teste t de Student não pareado, e o teste χ2foi empregado na comparação de variáveis categóricas. O valor de p<0,05 foi considerado estatisticamente significativo.Para a análise estatística, foi utilizado o software IBM Foram avaliados 1.729 pacientes; destes, 1.190 realizaram MR e 539 realizaram RET. A Do total de 1.729 pacientes, foram excluídos 10  nos quais não foi possível avaliar a indicação do exame. Não tinham indicação aparente para a realização do exame de retina conforme os critérios enumerados acima 58 pacientes ; 42 pacientes foram submetidos ao MR e 16 foram submetidos à RET. Na Em relação à modalidade de exame, 386 pacientes  apresentavam indicação para exame de retina e eram elegíveis para a modalidade RET. De todos os pacientes elegíveis para RET, 229  foram submetidos ao MR, o que correspondeu a 13,3% do total geral. Os motivos para a solicitação de exames neste grupo de pacientes foram acompanhamento de retinopatias estáveis  em 16 pacientes ; uso de medicação oral com potencial de toxicidade retiniana em 8 pacientes ; diagnóstico de diabetes em 83 pacientes ; diagnóstico ou investigação de GPAA em 86 pacientes ; diagnóstico de hipertensão arterial sistêmica em 36 pacientes .Os principais diagnósticos encontrados nos exames de retina estão expostos na No presente estudo, as principais indicações para a realização do exame de retina para pacientes avaliados em Unidade Básica de Saúde foram diabetes  e investigação de glaucoma ; nos portadores de diabetes, o exame estava normal em 34,3% das vezes. Os principais diagnósticos foram aumento da escavação papilar  e RD ; naqueles pacientes em que o resultado do exame foi normal, a principal indicação do exame foi a presença de diabetes . Considerou-se que em apenas 3,4% dos casos o exame foi solicitado sem indicação aparente. O MR foi o exame mais realizado ; no entanto, considerando todos os pacientes que eram elegíveis para a realização da modalidade RET, aproximadamente 60% destes foram submetidos ao MR.13 Como exemplos, podem-se citar a detecção de nevo de coroide como achado de exame e seu baixo risco de transformação maligna14 e alterações na periferia da retina não acompanhadas de sintomas, que geralmente são benignas e não demandam tratamento.15 No presente estudo, 121 pacientes (17%) apresentaram alterações retinianas periféricas (115 submetidos ao MR e 6 à RET).Atualmente, não há consenso quanto à necessidade da realização do exame de retina sob midríase em indivíduos que não apresentem sinais ou sintomas de doenças do segmento posterior ocular, ou que não tenham fatores de risco para o desenvolvimento de tais doenças, já que condições detectadas em exame de rotina sob dilatação pupilar e que geram mudança de conduta ou prevenção de desfecho são raras.American Academy of Ophthalmology (AAO) recomenda que um exame oftalmológico completo de base seja realizado em pessoas com 40 anos, mas não menciona especificamente a dilatação pupilar.16 O Conselho Brasileiro de Oftalmologia (CBO) elaborou protocolo que recomenda a realização de MR nas seguintes situações: pré-operatório de cirurgia de catarata ou de cirurgia refrativa; entopsias agudas ou crônicas; altas miopias; antecedentes familiares ou pessoais de descolamento de retina, trauma ocular e retinopatias hipóxicas .17A 19 ou em pacientes com sintomas de descolamento do vítreo posterior é indicação clara de MR, que permite avaliar a extrema periferia da retina, ao contrário da RET convencional.13 Tal discussão é válida se considerarmos apenas os retinógrafos convencionais, pois já há aparelhos de campo ultra-amplo que permitem avaliar a extrema periferia da retina; no entanto, atualmente, seu custo é muito alto, o que impede seu uso presente no sistema público de saúde. Futuramente, com a popularização de tais equipamentos, é possível que esta discussão se torne anacrônica.20Entretanto, na prática clínica, exames para avaliação da retina são solicitados como parte da investigação oftalmológica ou clínica complementar em diversas outras condições oculares ou sistêmicas que potencialmente afetam o segmento posterior do olho. Considerando as duas principais estratégias de exame da retina, o MR e a RET, não parece haver indicações claras quanto às situações em que uma ou outra estratégia está mais indicada; a escolha deve levar em conta fatores como a disponibilidade do exame, a relação custo-efetividade e a situação clínica específica. Por exemplo: a investigação de lesões predisponentes a descolamento de retina em pacientes com miopiaNa maior parte das indicações do exame, não houve diferença significativa entre a solicitação de uma ou outra modalidade diagnóstica, com as seguintes exceções: miopia maior que -3,00 dioptrias, investigação de baixa acuidade visual e hipertensão arterial, em que predominou significativamente a indicação de MR; e a investigação de glaucoma, em que predominou significativamente a indicação de RET. Tampouco houve diferenças importantes nas distribuições de diagnósticos obtidos por cada modalidade.20 já que é compatível com telemedicina e prescinde do especialista no momento do exame, havendo um custo elevado inicial para aquisição de equipamentos e montagem da estrutura, os quais tendem a se diluir posteriormente. Na situação estudada, o serviço já contava com os aparelhos, o que conferia a esta série um melhor perfil de custo-efetividade para a estratégia da RET. Em nosso meio, estudos avaliaram a adequação da RET associada à telemedicina para o alívio da demanda,21 principalmente no rastreamento da RD em um cenário de epidemia global de diabetes.22 No atual estudo, as RET foram realizadas sob midríase e atingiram uma boa qualidade técnica, sendo que apenas 1,5% das RET não permitiram leitura por má qualidade da imagem.Geralmente, os dois métodos diagnósticos para avaliação da retina estudados trazem resultados equivalentes e são estratégias intercambiáveis, com algumas situações em que a RET pode ser considerada o método de escolha em função do perfil custo-efetividade,23 Além disso, o sistema atual de obtenção das imagens, baseado em aparelhos de grande porte, deve passar por grande transformação, com a possibilidade de obtenção de imagens a partir de retinógrafos portáteis ou smartphones.24Adicionalmente, a avaliação por RET digital permite a interação com algoritmos de inteligência artificial, para o auxílio no rastreamento e na tomada de decisões clínicas, o que se apresenta como tendência para futuro.25 Deve-se ressaltar que, se, por um lado, o emprego da telemedicina pode representar a ampliação do acesso ao diagnóstico, por outro lado, o exame de retina é apenas uma parte do exame oftalmológico presencial, que inclui, ainda, anamnese, exame de refração, biomicroscopia, motilidade ocular extrínseca e tonometria.Durante a preparação deste artigo, o Brasil encontrava-se em meio a polêmica sobre a padronização da telemedicina, a partir de resolução do Conselho Federal de Medicina publicada em fevereiro de 2019 e revogada no dia 22 do mesmo mês (resolução 2.227/2018).Entre os pontos fortes deste estudo, podemos ressaltar o grande número de pacientes examinados em um mesmo centro ao longo de um período de aproximadamente 10 anos, e a avaliação de um dos cenários que corresponde à realidade em nosso meio. A apresentação destes dados pode auxiliar no planejamento de protocolos que objetivam melhor emprego de recursos. Entre as limitações do estudo, mencionamos o possível viés da escolha do exame devido a restrições de agenda, além de pacientes que tiveram o exame solicitado e não chegaram a realizá-lo. Outro viés diz respeito à documentação fotográfica de pacientes com diagnóstico ou suspeita de glaucoma, já que tinham a disponibilidade de um tipo especial de RET, a estéreo-fotografia de papila, que documenta o nervo óptico com maior aumento. Muitos pacientes desta categoria podem ter sido submetidos a esta modalidade, desta forma subestimando o diagnóstico de glaucoma ou suspeita de glaucoma na amostra estudada. Mesmo assim, o diagnóstico ou a suspeita de glaucoma foram duas das principais indicações de exames, e o aumento da escavação papilar foi o principal diagnóstico encontrado. Finalmente, há casos de pacientes que tiveram ambas as modalidades de exames solicitadas, mas apenas o primeiro exame a ser realizado foi considerado para a análise de indicações e resultados, o que constitui mais um viés em nossos resultados e conclusões.Os dados avaliados neste estudo apontaram que as principais indicações para solicitação do exame de retina foram o diabetes e a investigação de glaucoma, e os principais resultados dos exames foram o aumento da escavação papilar e a retinopatia diabética. Na ausência de diretrizes bem definidas para a solicitação de exames para a avaliação da retina, e sem critérios para a escolha da modalidade de exame da retina, os dados revelaram que, na prática diária, a modalidade de exame é escolhida geralmente de maneira intercambiável. Considerando que as diferentes estratégias estudadas possuem perfis distintos de custo-efetividade, sugere-se a criação de diretrizes quanto às indicações para a realização de exames de retina e a padronização da modalidade mais indicada em cada situação, de modo a otimizar recursos do sistema público de saúde.


In this paper, we investigate how subtle differences in hearing acuity affect the neural systems supporting speech processing in young adults. Auditory sentence comprehension requires perceiving a complex acoustic signal and performing linguistic operations to extract the correct meaning. We used functional MRI to monitor human brain activity while adults aged 18–41 years listened to spoken sentences. The sentences varied in their level of syntactic processing demands, containing either a subject-relative or object-relative center-embedded clause. All participants self-reported normal hearing, confirmed by audiometric testing, with some variation within a clinically normal range. We found that participants showed activity related to sentence processing in a left-lateralized frontotemporal network. Although accuracy was generally high, participants still made some errors, which were associated with increased activity in bilateral cingulo-opercular and frontoparietal attention networks. A whole-brain regression analysis revealed that activity in a right anterior middle frontal gyrus (aMFG) component of the frontoparietal attention network was related to individual differences in hearing acuity, such that listeners with poorer hearing showed greater recruitment of this region when successfully understanding a sentence. The activity in right aMFGs for listeners with poor hearing did not differ as a function of sentence type, suggesting a general mechanism that is independent of linguistic processing demands. Our results suggest that even modest variations in hearing ability impact the systems supporting auditory speech comprehension, and that auditory sentence comprehension entails the coordination of a left perisylvian network that is sensitive to linguistic variation with an executive attention network that responds to acoustic challenge. Hearing loss is associated with increased cognitive demand during speech comprehension. Here we used fMRI to measure brain activity while healthy adults with self-reported normal hearing listened to spoken sentences. We found that regions of right frontal cortex, outside of the traditional perisylvian language network, are more active for listeners with poorer hearing as measured with pure-tone audiometry. These findings suggest that executive attention varies with hearing ability, even in the absence of clinical hearing loss, during successful auditory sentence comprehension.Hearing ability varies considerably from person to person. Although individual differences in auditory sensitivity are most apparent as we age , variabiIt is noteworthy that young adults with hearing impairment are often unaware of it . In partStudies using functional MRI (fMRI) to investigate speech comprehension generally agree on the importance of bilateral temporal cortex for spoken word processing, with inferior frontal gyrus playing a more important role during sentence comprehension . SentencBehavioral work with older adults with age-related hearing loss has shown that the additional cognitive processing needed for successful speech recognition can require resources that might otherwise be available for other mental operations . The conIn the present study, we used fMRI to examine the consequences of differences in auditory sensitivity (hearing acuity measured outside of the scanner) for neural engagement during comprehension of spoken sentences in healthy adults with self-reported normal hearing. We hypothesized that additional neural resources would be recruited to compensate for the hearing decrement.n = 4), excessive head motion (n = 1), and lack of working memory data (n = 2), leaving us 35 subjects in total. All were self-reported right-handed native speakers of American English, with no known history of neurologic disorders. All participants reported themselves to have normal hearing, although a detailed history  was not collected. Participants’ hearing acuity was screened using pure tone audiometry and all fell within a clinically normal range, with a pure tone average (PTA) across 1, 2, and 4 kHz ranging from –5.0 to 23.3 dB HL  from the authors’ University community participated in the study. Participants ranged in age from 18 to 41 years old . Seven participants were discarded due to poor performance  Sentences were recorded by a male native speaker of American English.A subset of 24 sentences was vocoded with a single channel to serve as an unintelligible control condition with similar, speech-like characteristics.0 mapping sequence was acquired at the end of the scanning .Data were collected on a 3 T Siemens Trio scanner  installed with an 8-channel head coil. The field of view was angled ∼30° away from the AC-PC line. Scanning began with acquisition of a T1-weighted structural volume using a magnetization prepared rapid acquisition gradient echo (MPRAGE) protocol . Subsequently, 4 runs of blood oxygenation level–dependent (BOLD) functional MRI scanning were performed  using an interleaved silent steady state (ISSS) protocol ; Fig. 1BParticipants underwent 4 fMRI runs, each of which contained both spoken sentences and unintelligible noise (1-channel vocoded speech). Stimuli were presented at a comfortable listening level identified by each participant. Stimuli were presented 1 s after the silent period of the onset of ISSS using MRI-compatible high-fidelity insert earphones (Sensimetrics Model S14). For each sentence, participants were asked to indicate the gender of the character performing the action via button press as quickly and accurately as possible , 6 trials with 1-channel vocoded speech, and 6 trials of silence, totaling 36 trials (8.4 min per run). Sentences were distributed into four runs such that each stimulus associated with a base sentence was in one of the four runs, and the four types of stimulus sentences were equally distributed across the four runs. The order of conditions within each run was randomized. Each of the 96 sentences was presented only once.Before entering the scanner, participants received instructions and performed a practice session to ensure they understood the task. Once inside the scanner, but before scanning, participants confirmed intelligibility of spoken sentences at the intensity to be used in the main experiment by correctly repeating each sentence as it was presented. These sentences were not included in the main stimulus set. All participants were able to repeat back the sentences accurately, confirming audibility of the stimuli. Once set for a participant, the presentation level did not change during the course of the experiment, although there may have been modest variability in presentation level across participants (see Discussion).prelude and flirt routines from FSL version 5.0.5 . The rest of the preprocessing steps were performed using SPM12 : images were realigned to the first image in the series, coregistered to each participant’s structural image, normalized (with preserved voxel size) to MNI space using a transformation matrix generated during tissue class segmentation  and a cluster-level threshold of p < 0.05 (FWE-corrected) across the whole brain based on cluster extent and Gaussian random field theory (http://www.humanconnectome.org/software/connectome-workbench.html) and slices using MRIcron .All whole-brain results were thresholded using a cluster-forming voxel-wise threshold of d theory . Results MRIcron . UnthresZ = –2.807, p = 0.005) and the interaction between syntactic complexity and PTA . A detailed summary of all variables is listed in The comprehension accuracy across four different sentence types is shown in r = –0.38, p = 0.02), but there was no relationship between PTA threshold and bias .Next, given that our behavioral task involved a two-alternative forced choice (2AFC) task, we calculated signal detection theory measures  to see if there was any behavioral pattern associated with poor hearing ability. To this end, we performed a correlation analysis which revealed that participants with higher PTA thresholds had lower sensitivity , was found in left inferior frontal gyrus (We next compared fMRI activity related to syntactic complexity (object-relative sentences vs. subject-relative sentences) and position of the phrase insertion (early vs. late). We found significant differences in the former comparison in which a significant cluster emerged in the posterior portion of left superior temporal gyrus. An additional cluster, marginally significant in cluster-based correction . We then performed a series of univariate regressions in which PTA was regressed against each of age, working memory, and behavioral accuracy separately, with the residuals entered into the whole-brain regression. The right aMFG activity still remained significant . Lastly,p < 0.005, extent cluster size = 30), more clusters were found throughout the frontoparietal attention network, including the right superior frontal gyrus and right posterior STG .During everyday conversation, listeners are generally successful in extracting meaning from speech that varies in its linguistic complexity. Here we have shown that successful sentence comprehension depends in part on the integrated functioning of two networks: the core, left frontotemporal sentence processing network that increased activation depending on syntactic demands; and right anterior middle frontal gyrus, part of the frontoparietal attention network, where activation varied as a function of individual differences in hearing acuity irrespective of syntactic demands. Our data reveal that individual differences in hearing acuity mediate right frontal recruitment even in young adults despite their hearing falling within a range commonly considered to be clinically normal. We discuss the implications of these findings below.We varied linguistic challenge using subject-relative versus object-relative center-embedded clauses. Comprehending syntactically complex sentences is routinely associated with increased activity in frontotemporal regions, most notably large regions of left frontal cortex and left posterior temporal cortex . Here weMuch prior work has studied the comprehension of grammatically challenging sentences using written materials. The assumption has been that the left perisylvian language network supports a supramodal syntax-processing mechanism . HoweverAlthough it is useful to think about the core frontotemporal regions involved in understanding intelligible sentences , this coAlong with these observations comes mounting behavioral evidence that changing the acoustic clarity of the speech signal has cognitive consequences . For exaAlthough past research has illustrated cognitive consequences of hearing loss in older adults, in the present study we found that differences in hearing acuity in normal-hearing adults can have a significant impact on the brain activation associated with sentence comprehension. That is, the right anterior middle frontal gyrus’s activity was greater in participants whose hearing acuity was poorer. This is particularly intriguing in that the hearing acuity was measured outside of the scanner, and the sound intensity of sentence stimuli was adjusted to the comfortable level during scanning for each individual. This suggests that internal hearing challenge weighs more than mere adjustment of volume to the comfort level with regard to speech comprehension. Importantly, this relationship held true during correct trials, but not error trials, indicating that upregulation of right aMFG may lead to successful speech comprehension for those who have mild hearing decrement despite still falling within a range defined as clinically normal hearing for speech .One of our main interests was to investigate the degree to which brain regions outside the core speech network are recruited to facilitate comprehension. Two particularly relevant systems are the cingulo-opercular and frontoparietal executive attention networks . In our The cingulo-opercular network includes the dorsal anterior cingulate and bilateral frontal operculum (and/or anterior insula). Consistent with its role in error monitoring, activity in the cingulo-opercular network is frequently seen in speech comprehension tasks under conditions where intelligibility is reduced. This includes single words in noise  and noisBy contrast, the frontoparietal attention network includes bilateral inferior parietal cortex and dorsolateral prefrontal cortex, and is frequently implicated in flexible application of task demands , particuIn the present study, we employed an advanced auditory fMRI protocol, ISSS, which allowed multiple time points of data acquisition following the presentation of a stimulus during a silent period. From a data-analytic perspective, this posed a unique challenge such that the conventional modeling scheme  is not straightforward. As described in Methods, we used an FIR model as an initial step to estimate an unbiased response at each time point. Then, by taking the integral of all beta estimates across consecutive time points, we computed a summed positive response area (SPA). Although this approach may be less sensitive than FIR , one advSecond, the sound presentation level for each participant was chosen after a few rounds of adjusting the intensity that was most comfortable before the experiment. Once set, the volume was fixed over the course of the study. We adjusted the presentation volume for each participant to ensure comfort and audibility but acknowledge that this approach potentially changed the stimulation level across participants. However, we note that this did not work against our hypothesis and finding, in that PTAs still predicted both behavioral performance and activity in right aMFG. Last, despite finding that right aMFG was the only significant region across univariate and bivariate regression analyses predicted by PTA, we acknowledge that the right aMFG cluster did not survive significance when the PTA metric was regressed against all variables taken together, including age, working memory, and accuracy. This is presumably due to the relatively small sample size for the whole-brain regression analyses. Nonetheless, our several confirmatory analyses involving error and noise trials and significant correlation result of PTA and right aMFG activity without outliers suggest that right aMFG plays a role in compensating for modest hearing decrement in young adults.Although noise-induced hearing loss is often thought of in terms of exposure to explosive blast, power tools, recreational vehicles, or unprotected industrial noise , risks t


Macaca thibetana) at Mt. Huangshan, China. Our results showed that females with infants received more grooming than females without infants. After her infant was handled, mother females received more grooming than they did during daily grooming interactions. However, with the increasing number of infants within the social group, both the grooming that mothers received and the grooming that non-mothers invested for handling infants decreased. We also found that non-mothers invested more time in grooming to gain access to younger infants than older infants. Our results provide evidence that infants are social commodities for both mother and non-mother females. Mothers use infants for obtain grooming and non-mothers use grooming to gain access to infants. The current study implies a bidirectional and complex interchange pattern between grooming and infant handling to compensate for the dyadic grooming disparity in non-human primates.In some non-human primates, infants function as a social tool that can bridge relationships among group members. Infants are a desired commodity for group members, and mothers control access to them. The biological market theory suggests that grooming is widespread and represents a commodity that can be exchanged for infant handling. As a limited resource, however, the extent to which infants are interchanged between mothers  and non-mothers  remains unclear. In this study, we collected behavioral data to investigate the relationship between grooming and infant handling in free-ranging Tibetan macaques ( While female attraction to infants represents a common feature in non-human primate species, maternal responses to infant handling show a certain degree of variability . In somePapio cynocephalus ursinus), Rhinopithecus roxellana), indicating that infant handling might be interchanged for grooming. Infant handling is also reported as a social commodity to interchange for affiliation, e.g., embracing in spider monkeys (Ateles geoffroyi yucatanensis)  .Cebus apella nigritus), P. anubis) (Macaca fascicularis)  , long-tacularis) , and golcularis) .These previous studies suggest that both grooming and infant handling opportunities are valuable commodities in primates. Infant handling consists of an infant and adult female other than its mother. The groomer  may interchange grooming to gain access to the groomee’s infant . Accordingly, as a limited-competition resource, infants could be interchanged between the groomee  and groomer . However, the extent to which individuals perform grooming for infant handling or provide infant handling for grooming among females remains unclear.M. thibetana). Tibetan macaques live in multi-male-multi-female social groups (mean group size=33.8±6.79), with female philopatry and male dispersion  females with infants will be more attractive than females without infants, and females will receive more but provide less grooming after giving birth than before parturition; (2) with an increase in the number of infants, females with infants will receive less grooming from females without infants; (3) females with infants will receive more grooming if they first allow their infant to be handled; if grooming is an effective way to gain access to an infant, (4) females will obtain more infant handling opportunities after grooming the infant’s mother than they have under baseline social conditions.This study was conducted at Mt. Huangshan National Reserve in Anhui Province, China. The reserve is a World Culture and Nature Heritage site and well-known tourist destination, as well as research site for the study of Tibetan macaques.The study site can be found within the reserve in an area known as the “Valley of the Monkeys”. There are two groups at the site: Yulingkeng A1  and Yulingkeng A2 (YA2). Matrilineal kinship is known from historic and demographic data collected daily since 1986 . The tarThis study was conducted from July 2016 to January 2017 and from March to May 2017. All behavioral data were collected during an intensive study period over 201 days . The social group was followed from dawn to dusk, and behavioral observations began at approximately 0700–0800 h and ended at 1700–1800 h each day (depending on the time of year). The observer maintained an observation distance of 5–10 m from the monkeys.Focal animal sampling and continuous recording  were used to score the daily activity of the focal individual , with thTo investigate whether non-mothers were more likely to handle infants after grooming their mothers, we collected post-grooming (PG) samples. The PG samples consisted of 15-min focal observations of a non-mother who had just groomed a mother. To investigate whether infant handling by non-mothers increased subsequent grooming investment given to mothers, we collected post-infant handling (PH) samples. The PH samples consisted of 15-min focal observations of a non-mother who had just handled an infant of a mother. On the next day, at the same time, we conducted 15-min matched control (MC) focal observations matched with a PG or PH sample, with no grooming or infant handling preceding the focal observation . We collad libitum sampling to collect data on duration of all grooming bouts between mothers and non-mothers that involved infant handling. We categorized an interaction as a grooming-infant handling interchange if a non-mother groomed a mother and handled her infant. This could occur in any order and any number of times. The interaction finished when the two individuals moved >5 m away from each other. We measured the total duration of grooming until the two females departed each other. We recorded the dyadic social relationships immediately when an interaction ended. According to We used ad libitum sampling to record aggressive and submissive behaviors to determine dominance relationships. Aggressive interactions were defined as an individual threatening, chasing, slapping, grabbing, or biting another individual  and infant handling frequency (times/h). We used a one sample Kolmogorov-Smirnov test to examine whether the data conformed to normal distribution (P>0.05).We reported baseline data as mean±t-tests to analyze whether mothers were groomed for longer periods after giving birth than before parturition, and whether mothers groomed non-mothers less after giving birth than before parturition.We used the baseline data and calculated the duration of grooming received by mothers from non-mothers and given to non-mothers by mothers before parturition and six months after giving birth. Data were compared using paired t-test to compare the duration of grooming between focal samples and PH samples, and between MC samples and PH samples to determine if non-mothers handling infants promoted the non-mothers to groom mothers. We used paired t-test to compare the frequency of infant handling between focal samples and PG samples, and between MC samples and PG samples to determine if non-mothers grooming mothers promoted non-mother infant handling.We collected data on 11 of the 15 females investigated for PG and PH. No data were collected for three adult females , who were older and less socially active in regard to infant handling and did not give birth or become pregnant during the study. One subadult female (THX) was not observed to engage in a grooming-infant handling interchange. We used paired ad libitum data collected on grooming-infant handling interchange to investigate whether the number of infants per female was negatively correlated with duration of non-mothers grooming mothers during the interaction. We used linear regression to determine relationships between grooming and the number of infants per female.We used the We analyzed grooming-infant handling interchange data to elucidate the effect of infant age on the duration of non-mothers grooming mothers during the interaction. We used linear regression to determine the relationship between infant age and duration of non-mothers grooming mothers. We assessed individual dominance rank by calculating David’s Score (DS). We also calculated linearity for the obtained dominance hierarchy  Rank dist-tests to compare the duration of non-mothers grooming mothers between kin and non-kin.We analyzed grooming-infant handling interchange data and used linear regression analysis to test the relationship between rank distance and duration of non-mothers grooming mothers. To investigate whether kinship between non-mother and mother affected the duration of non-mothers grooming mothers when infant handling, we used paired To account for potential bias caused by pseudoreplication, we used factorial ANOVA to test for variation across individuals and number of infants, infant age, and rank distance on the duration of non-mothers grooming mothers. We found a significant effect of number of infants, infant age, and rank distance on grooming duration, but no significant effect on individuals or interaction effects. We found no evidence that individual variation existed and therefore no support that individual idiosyncrasies solely accounted for the results. Thus, pseudoreplication did not seriously affect the results.During the study period, we collected 90 valid PG-MC samples, 86 valid PH-MC samples, and 148 grooming-infant handling interchanges.SE) was significantly longer than after birth (0.62±0.07 min/h) , whereas the mean duration of non-mothers grooming mothers after birth (1.27±0.17 min/h) was significantly longer than that before birth (0.66±0.09 min/h)  (The mean duration of mothers grooming non-mothers before birth (1.04±0.05 min/h) (mean±P=0.008) .SE). After non-mothers handled infants of mothers, the mean duration of non-mothers grooming mothers was 3.02±0.22 min/h (mean±SE). The duration of grooming was significantly higher in PH samples than in focal samples . In MC sample observations, the mean duration of non-mothers grooming mothers was 1.74±0.08 min/h (mean±SE). The duration of grooming was significantly higher in PH samples than in MC samples   .P<0.001, R2=0.390, df=147)  .SE). After non-mothers groomed mothers, the mean frequency of non-mother infant handling was 6.20±0.65 times/h (mean±SE). The mean frequency of infant handling was significantly higher in PG samples than in focal samples . In MC sample observations, the mean frequency of infant handling was 2.60±0.36 times/h (mean±SE). The mean frequency of infant handling was significantly higher in PG samples than in MC samples   .P<0.001, R2=0.402, df=147)  . The durP=0.001, R2=0.076, df=147)  .t-test: t=0.758, df=4, P=0.491).There was no significant difference in the duration of non-mothers grooming mothers when infant handling between kin and non-kin (paired R. roxellana) (P. anubis) (R. roxellana) and long-tailed macaques (M. fascicularis)  and groomer . However, the extent to which individuals groom in exchange for infant handling or offer infant handling in exchange for grooming among females remains unclear. In this study, we found that mothers received more grooming from non-mothers after birth than before birth, and that mothers groomed non-mothers less after birth than before birth. These results supported the prediction that females with infants are more attractive than females without infants and that females will receive more but provide less grooming after birth than before parturition. These findings are similar to that reported for golden snub-nosed monkeys (xellana) . Further anubis) . We alsocularis) . Thus, wA single behavioral exchange may not explain all behavioral relationships among individuals. In the case of reciprocity, pairs of actors are expected to form long-term and predictable social relationships so that, on average, the overall costs and benefits to each are relatively equal over time . In contM. fascicularis), tufted capuchin monkeys (Cebus apella nigritus), sooty mangabeys (Cercocebus atys), and vervet monkeys (Chlorocebus aethiops)  and long-tailed macaques (M. fascicularis)  . These rethiops) , with inethiops) . Under aethiops) . In Tibecularis) .Dominance hierarchy is a factor that has considerable influence on social interchange in non-human primates. Dominance relationships may make social commodities cheaper for higher-ranked individuals and more expensive for lower-ranked individuals . In TibeIn Tibetan macaques, we found the interchange between grooming and infant handling to be bidirectional and to change with the age and number of infants. The interchange relationship between grooming and infant handling is an important part of social relationship maintenance and group stability in primate societies. It not only helps us to understand the characteristics of behavioral adaptation in adult individuals, but also highlights the social functions of infants.


Retinopathy of prematurity (ROP) is an ocular disorder which affects infants born before 34 weeks of gestation and/or with birth weight of less than 2000 grams. If not detected on time and appropriately managed, it can lead to irreversible blindness.The retinal blood vessels first appear between 15–18 weeks of gestation. These vessels grow outwards from the central part of the retina and extend towards the retinal periphery. The nasal part of the retina is fully vascularised by 36 weeks of gestation followed by the temporal retina which is completely vascularised between 36–40 weeks of gestation age . FollowiThe development of ROP can be divided into two phases - an initial phase of delayed growth of retinal vessels followed by a second phase of retinal vessel proliferation .At birth the lungs of an infant born preterm are immature placing him/her at a high risk of developing abnormally low level of oxygen in arterial blood.To overcome this, the newborn infant is given supplemental oxygen in NICU. Prior to 32 weeks of gestation, the retina is very immature and the retinal metabolic demand is low. This excess oxygen creates retinal hyperoxia and oxygen toxicity, inhibiting the production of VEGF. This is followed by temporary stopping or stoppage of normal retinal growth, and constriction of new immature vessels. As a result, there is a reduction of blood supply to retinal tissue and shortage of oxygen needed for metabolism.With increasing age of the preterm infant the retina matures. There is an increase in metabolic demand and oxygen consumption by the retina, creating a relative decrease in oxygen level. This promotes increase in the level of vascular endothelial growth factor (VEGF), triggering the formation of new blood vessels along the inner retinal surface. A demarcation ridge develops along the retina that separates the central vascularised retina from the peripheral avascular retina .The growth of retinal blood vessels at this stage may restart normally or may progress to significant ROP as seen by an abnormal growth of retinal vessels into the vitreous and over the surface of the retina. These new vessels are weak and underdeveloped failing to fulfill the oxygen demand of retinal tissue resulting in continuous growth of abnormal vessels. There is leakage of fluid or blood from these weak blood vessels. If not treated on time this can result in scarring or traction of the retina leading to retinal detachment and blindness .


Objective: China is experiencing the world's largest urbanization. There are two primary types of urbanization in China: rural-to-urban migration and in situ urbanization, represented by Zhejiang Shangyu (SY) and Jiangsu Nanjing (NJ), respectively. Our aim is to compare changes in the prevalence of metabolic disease between these two types of urbanization in China.Methods: This is a cross-sectional study derived from the SPECT-China 2014 study. This study includes subjects and metabolic parameters from SY and NJ. Furthermore, biochemical and anthropometric indexes were taken into consideration and compared between the areas of interest.Results: The prevalence rates of diabetes, prediabetes and healthy subjects were 6.5, 17.9, and 75.7% in SY and 16.0, 31.0, and 53.0% in NJ, respectively. Industrial and agricultural jobs accounted for 77.9% and 32.0% of employment in SY and NJ, respectively. Fasting plasma glucose (FPG) was higher in SY than in NJ; however, HbA1c was lower in SY than in NJ. There was a significant difference in nonalcoholic fatty liver disease (NAFLD) and healthy subjects between SY and NJ (P < 0.05). Significant differences were also found with respect to body mass index (BMI), waist circumference (WC) and hip circumference (HC) between these two locations (P < 0.001). Logistic regression analysis revealed that the prevalence of prediabetes, diabetes, overweight, obesity and dyslipidemia was higher in NJ than in SY.Conclusions:In situ urbanization has notably changed occupational distribution. The prevalence rates of diabetes, obesity, and NAFLD were increased in rapidly urbanized areas. Thus, more attention should be paid to rapidly urbanizing areas to reduce the prevalence of metabolic disease. The prevalence of non-communicable diseases (NCDs) has increased rapidly worldwide . In 2005in situ urbanization of rural areas , representing a population-based cross-sectional survey on the prevalence of metabolic diseases and risk factors in eastern China. For this study, 1,569 subjects in Zhejiang Shangyu (SY) and 1,427 subjects in Jangsu Nanjing (NJ) were recruited. Adults who had lived in their current residence for 6 or more months were selected and enrolled in our study. Exclusion criteria included the following: excessive drinking (n = 159), self-reported viral hepatitis (n = 30) and use of corticosteroids (n = 10). Finally, the current study was based on a total of 2,797 subjects .This report describes a substudy of SPECT-China , but during the past 10 years, they experienced different development speeds. NJ rapidly changed to an urban area by in situ urbanization, whereas SY developed relatively slowly.Zhejiang Shangyu (SY) is a county-level city. The selected three natural villages were gradually developed. In this situation, urbanization was gradually achieved by urban expansion and migration from rural to urban areas. Before 2007, the Jiangsu Nanjing (NJ) Xianhemeng community was composed of three natural villages. In 2007, the people who lived in these three villages were voluntarily relocated to form a large community. Villagers lost their land and became urban residents, and urbanization was achieved by This study protocol was approved by the Ethics Committee of Shanghai Ninth People's Hospital. Written informed consent was obtained from all participants.Blood sample collection and biochemical indexes were described previously . Liver u2). BMI ≥ 28 kg/m2, 24 kg/m2 ≤ BMI < 28 kg/m2, and BMI < 24 kg/m2 were defined as obesity, overweight and normal, respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as fasting serum insulin (mIU/L) × FPG (mmol/L)/22.5. Occupation was defined as follows 1, farmer; 2, worker; 3, soldier; 4, cadres; 5, teacher or doctor; 6, self-employed; 7, service staff; 8, homemaker; 9, retired; 10, unemployed; 11, student; and 12, other. Finally, these occupations were summarized as industry (including 2), agriculture (including 1), service industry , unemployed , and other .Diabetes was defined as self-reported diabetic history or HbA1c 6.5% or greater. Prediabetes was defined as HbA1c between 5.7 and 6.4%. NGT was defined as HbA1c < 5.7% . AccordiU test and independent sample t-test were used for continuous data with skewed distribution and normal distribution between SY, and NJ. The Pearson chi-square test was used for categorical variables. We used linear regression analyses to investigate the association between metabolic indexes (continuous variable) and the urbanization level. Model 1 was adjusted for age and sex. Model 2 was further adjusted for HbA1c, BMI, systolic blood pressure (SBP), high density lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride (TG). Because TG exhibited a skewed distribution, it was log transformed. Logistic regression analysis was also performed to investigate the association of metabolic diseases (dichotomous variable) with the urbanization level. Prediabetes, diabetes, overweight, obesity, and dyslipidemia were dependent variables. The model was adjusted for age, sex, diabetes, weight status, hypertension, and dyslipidemia. All analyses were two-sided, and P < 0.05 was considered significant.Statistical analysis was performed using IBM SPSS Statistics, Version 22 . Continuous variables were expressed as the mean ± SD. Categorical variables were expressed as a percentage (%). The Mann-Whitney P < 0.001) and DBP   and 872 females (age 53.53 ± 13.57 years), in SY and 1,235 subjects, including 302 males (age 56.47 ± 12.84 years), and 933 females (age 55.16 ± 12.42 years), in NJ were recruited. The prevalence rates of diabetes, prediabetes, and normal people in two locations were 6.5, 17.9, and 75.7% (SY) and 16.0, 31.0, and 53.0% (NJ), respectively. There was a significant difference between SY and NJ in SBP . The proportions of individuals in the service industry were 6.5% and 18.0% in SY and NJ (P = 0.01), respectively. Moreover, the unemployment rates were 12.1% and 37.8% in SY and NJ (P < 0.001), respectively, , except in subjects older than 70 years. This trend was more apparent in females than in males. In contrast, HbA1c was lower in SY than in NJ  for all age and sex subgroups. Moreover, there was no significant difference in HOMAIR between SY and NJ . HDL was significantly decreased in NJ . This trend existed in all age and sex subgroups. TC was significantly elevated in NJ only in females—this difference did not exist in males . This difference existed both in males and females. As the age increased, the proportion of normal subjects decreased, but the proportion of those with steatosis or NAFLD increased. However, in people over 70 years old, the proportion of fatty liver decreased, whereas the proportion for normal liver increased in both NJ and SY. Additionally, 21.0 and 24.6% subjects had steatosis in SY and NJ, respectively, (P = 0.55) . WC and HC in SY were significantly lower than those in NJ . Moreover, these differences existed in all age groups and between the sexes. However, NC in SY was lower than in NJ only in males (P < 0.001)  of prediabetes and diabetes was 2.475  and 3.287  in NJ (adjusting for exclusion of FPG and HbA1c), respectively. Compared with SY, the OR of overweight and obesity was 2.491  and 2.909  in NJ (adjusting for exclusion of BMI), respectively. Dyslipidemia was 87.5% higher in NJ than in SY   were significantly reduced in NJ. Thus, more people were engaged in the service . Meanwhile, villagers in NJ lost their farmland, and 36.3% became unemployed or retired early. Finally, residents in NJ had dramatically decreased occupational PA than SY. PA mainly includes occupational PA, commuting PA and leisure time PA , 16. OccIn our study, the prevalence of diabetes was 16.5% in NJ, which is higher than that previously reported both in urban (14.3%), and rural (10.3%) areas . The subIncreased LDL and TG and decreased HDL were detected in NJ. However, TC in NJ was higher than that of SY in females but not in males. In people over 70 years old, the proportion of fatty liver decreased, and the proportion of normal liver increased in both NJ and SY. However, both LDL and TC reached their peak at 60 years, after which they decreased. Dyslipidemia is closely related to NAFLD , 27. ThiBMI in NJ was greater than that in SY for all age and sex subgroups. The overall NC was higher in NJ than in SY. However, this trend was more obvious in males. The WC and HC in NJ were higher than in SY. Moreover, the residents in NJ had higher HbA1c, LDL and TC, which were all risk factors for cardiovascular diseases .There are several limitations to our study. First, we did not test PPG in this study, although we could estimate it using FPG and HbA1c. Second, we did not apply metabolic equivalent of task (MET). Third, passage from rural work activities to urban activities is associated with loss of seasonal rhythms and with sleep changes. Sleeping too little or too much can influence insulin resistance and obesity. However, we did not measure sleep duration in our article , 30. ForIn conclusion, China is undergoing profound changes in urbanization today. The prevalence of diabetes, obesity, and NAFLD are increased in rapid urbanized areas. Occupational alterations may play a role in this process. Thus, greater attention should be paid in these areas to reduce the prevalence of metabolic disease. Additionally, social determinants that may predict differences in cardiometabolic risk should be addressed.YL and NW designed and supervised this investigation. BH and YiC performed this investigation. QL, CZ, and YinC contributed to the data collection. FX and JC provided technical or material support. All authors read and approved the final manuscript.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.