Congenital unilateral sensorineural hearing loss (uSNHL) is associated with speech-language delays and academic difficulties. Yet, controversy exists in the choice of diagnosis and intervention methods. A cross-sectional prospective design was used to study hearing loss cause in twenty infants with congenital uSNHL consecutively recruited from a universal neonatal hearing-screening program. All normal-hearing ears showed ≤20 dB nHL auditory brainstem response (ABR) thresholds (ABRthrs). The impaired ear median ABRthr was 55 dB nHL, where 40% had no recordable ABRthr. None of the subjects tested positive for congenital cytomegalovirus (CMV) infection. Fourteen subjects agreed to participate in magnetic resonance imaging (MRI). Malformations were common for all degrees of uSNHL and found in 64% of all scans. Half of the MRIs demonstrated cochlear nerve aplasia or severe hypoplasia and 29% showed inner ear malformations. Impaired ear and normal-hearing ear ABR input/output functions on a group level for subjects with ABRthrs < 90 dB nHL were parallel shifted. A significant difference in interaural acoustic reflex thresholds (ARTs) existed. In congenital uSNHL, MRI is powerful in finding a possible hearing loss cause, while congenital CMV infection may be relatively uncommon. ABRs and ARTs indicated an absence of loudness recruitment, with implications for further research on hearing devices. Congenital unilateral sensorineural hearing loss (uSNHL) is a chronic condition affecting approximately 1 in every 2000 newborns ,4,5). ThControversy exists in the choice of diagnostic methods for children with uSNHL. For example, some argue for using imaging ,13,14, wMalformations of the auditory system are more common in congenital uSNHL compared to bilateral SNHL ,17. The The congenital cytomegalovirus (cCMV) infection is believed to be the leading non-genetic cause for SNHL during the last few decades, with a prevalence of up to 20–30% in SNHL ,23,24. IResearch of auditory profiles or hearing function in relation to etiology is lacking. Most research on etiology and auditory profiles in uSNHL focuses on cochlear implant (CI) candidates with profound uSNHL, i.e., single-sided deafness (SSD) e.g., ,31), and, and31])The aim was to describe congenital uSNHL (ranging from mild to profound) in infants, focusing on the causes, hearing function and the affected auditory mechanisms by using a prospective study design and a comprehensive test battery. Tests included MRI, cCMV infection testing, acoustic reflex threshold (ART) measurements to investigate middle ear, inner ear and neural function e.g., ,37), and, and37])The subjects were recruited during the years 2019–2020 from the bedside UNHS program in Region Stockholm, which is based on multiple transient-evoked OAE (TEOAE) recordings and an automatic ABR (aABR). The UNHS program has been described previously  ,43,44, wEligible subjects were invited to participate in two research visits. ABRs, TEOAEs, distortion-product OAEs (DPOAEs), tympanograms, and ARTs were recorded at the first visit. The ABRs, TEOAEs and DPOAEs were recorded in an audiometric test room with low ambient sound levels, allowing determinations down to −10 dB HL (ISO8253-1 2010). The tympanograms and ARTs were measured in the audiometric test room or a quiet room. Otomicroscopy was performed by an experienced otologist to exclude middle ear disease. An oral case history was obtained from the infants’ parents for additional information including parents’ knowledge about relevant medical and development history, including prenatal and perinatal history. Testing for cCMV followed as soon as possible. The visit took approximately 2.5–3 h.At a second research visit, all eligible subjects were invited to the MRI of the auditory system (inner ears and cochlear nerve).This study was approved by the Swedish Ethical Review Authority (no: 2018/1500-31). Written informed consent was obtained from all parents with child custody.Several recruitment steps were undertaken with the aim of inviting all children born with uSNHL and excluding all children with temporary hearing loss, e.g., otitis media with effusion (OME). Inclusion criteria comprised: (1) One ear passing and one ear failing TEOAE UNHS; (2) An ABR threshold (ABRthr) > 30 dB nHL in the IE; and (3) An ABRthr of ≤20 dB nHL in the NE.M.J. (first author) was notified when a neonate was suspected of having a unilateral hearing loss, i.e., failed several TEOAE tests in one ear and passed in the other ear, passed aABR screening in one ear  and failed in the other ear (>30 dB nHL). TEOAE pass criteria included: ≥70% whole wave reproducibility, signal-to-noise ratio (SNR) ≥4 dB in at least three of the upper four wide-frequency bands provided by the ILO instrument, and ≥50 sweeps. The neonate’s families were informed of the study and invited to the next step in the study recruitment process at the first audiologic test visit following UNHS if the ABR showed thresholds >30 dB nHL in the IE and a SNHL was alleged , tympanograms, TEOAEs, and sometimes bone-conduction ABR), and ≤25 dB nHL in the NE.In total, 48 out of 68 potential subjects based on the UNHS were excluded at the first audiologic test visit following screening or, in a few cases, at the first research visit as they did not fulfill the study inclusion criteria. This was typically due to OME that fully explained the elevated ABRthr in the IE, or an ABRthr ≤ 30 dB nHL in the IE, or bilateral hearing loss (≥25 dB nHL in both ears).Thus, 20 infants with congenital uSNHL were invited to the study, and the 20 families all consented to participate in the study  with Eclipse EP25 .The ABR was recorded in 10 dB steps whenever possible, from 70 dB nHL down to the threshold or 20 dB nHL minimum. The 70 dB nHL level was chosen as the main supra-threshold level for analysis of the ABR I–V interval. If the ABR waves I and V could not be discerned at 70 dB nHL, the input level was increased in 10 dB steps up to a maximum of 80 dB nHL for the NE, and 90 dB nHL for the IE.The response quality was enhanced by the use of up to 10,000 sweeps at stimulus levels close to the ABRthr, and ≈2000 sweeps for the other stimulus levels. Calibration of 100 µsec clicks was performed according to ISO389-6 (2007) in an occluded ear simulator IEC60318-4 (2010) ,48.Ag/AgCl electrodes were placed on left and right mastoids , and the forehead  for differential recording between ipsilateral mastoid (noninverting) and the forehead (inverting). The subject was placed in a supine position in the parent’s arms or in a baby carrier. Lights in the audiometric test room were turned off during the ABR recordings in order to minimize electric interferences.E.B. determined all the ABR waves, blinded to which subject and ear that was evaluated. The ABR latencies were determined using narrow-band filtering , thereby obtaining a well-defined vertex-positive peak.ρ) was objectively determined in the time domain (1–15 ms) for the entire ABR [ρ was <70% . The wa minimum .Contralateral masking was applied when needed .The TEOAEs were recorded in the non-linear quickscreen neonate diagnostic mode with Echoport ILO288 USB-II . For details on the non-linear stimulus paradigm see . The Ech1-f2 cubic distortion product component was measured with a frequency ratio of the primaries of 1.22 (f2/f1). The stimulus consisted of two equal-level sinusoids with an expected sound pressure level of 75 dB SPL at the tympanic membrane  in dB. The NE was tested first in 63% of subjects, and the right ear first in 53% of subjects.The DPOAEs were recorded using the same test setup as the TEOAEs with Echoport ILO288 USB-II . The 2fy, e.g., ). The DPTympanograms and ARTs were recorded in both ears with GSI Tympstar  to primarily study the middle ear system and the function of the reflex arc. The ART was elicited ipsilaterally at tympanic peak pressure and at the stimulus frequency of 1000 Hz, using an ascending method in steps of 5 dB with a maximum of 105 dB HL (as recorded in a 2-cc coupler). The criterion for a reflex response was a repeatable compliance change corresponding to 0.02 mL or greater, supported with an impedance growth at a higher stimulus level.Subjects were excluded from MRI if they were too ill for sedation with dexmedetomidine, which was determined in two steps, first by the responsible otologist (E.K.), then by the MRI team physician. One subject was excluded from MRI due to a congenital heart abnormality. Another 5 out of 19 subjects declined MRI participation .n = 8, or Siemens Prisma, Erlangen, Germany, n = 5), the exception being for S3, where a 1.5T scanner was used , as a back and spine MRI was prioritized additional to the auditory system MRI.All but one of the 14 MRI scans were assessed with 3T scanners  and T2-weighted images (T2WI) of the temporal bone, as well as sagittal T1WI, transversal T2-weighted Fluid Attenuated Inversion Recovery images (T2 FLAIR), diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) of the brain.The 1.5T scan was performed using a protocol designed for the temporal bone. The inner ear was assessed using a transversal T2 3D FIESTA sequence with 0.6 mm thickness, and the cochlear nerve by making oblique sagittal reconstructions from this sequence. The scan also included sagittal and coronal T2WI as well as transversal T1WI, T2 FLAIR and DWI of the brain.The MRI results were reviewed by one or two experienced neuroradiologists or head-neck radiologists, and later all results were double checked by K.E., an experienced head-neck radiologist.A blood sample was taken from the mother for CMV testing as soon as possible after the study inclusion. If the mother had a positive CMV-test (lgG and/or lgM antibodies) the child’s newborn dried blood spot (DBS) card was then analyzed for CMV DNA with the polymerase chain reaction (PCR) technique. Exceptions were made from the study protocol for two subjects where the DBS cards were analyzed directly, as the mothers had not yet taken the blood sample after several months, despite repeated reminders, and one subject had already been CMV tested with a blood sample the same day as birth.All the statistical analyses were performed with Statistica version 13.5 , except linear mixed modelling, which was performed with R version 3.4.2 .Mean and SD are primarily presented in this study for easy comparison with previous studies, although medians and interquartile ranges (IQRs) are presented when Kurtosis and Skewness were clearly different from zero, e.g., for ARTs and ABRthrs.Nonparametric tests were used for statistical testing, due to small sample sizes.t-tests).Due to the parallel-shifted IE and NE ABR I/O functions on the group level, a post hoc analysis with linear mixed modelling of ABR amplitude was performed , with the ear (NE/IE) and stimulus level as fixed effects and the subject as the random variable  . SubjectThe median chronological age at the first research visit, and the diagnosis of congenital uSNHL, was 2.2 months . The oton = 20 subjects).All subjects slept during the ABR recording. The maximum electrode impedances (33 Hz square wave) were low with a median of 1.5 kΩ , with a wave-V reproducibility of >73% within a time window of 1–1.5 ms encompassing the wave (median ρ = 97%).ABRthrs of 20 dB nHL were recorded in all NEs (n = 20). In 8 subjects (40%), no ABR waves could be discerned in the IE at 90 dB nHL .The median ABRthr was 55 dB nHL in the IE . For thp = 0.26, n = 9). However, the interaural between-subject variability was large (n = 17) and 4.92 ± 0.34 ms in the IE (n = 8). At 80 dB nHL, it was 4.82 ± 0.31 ms in the NE (n = 8) and 4.81 ± 0.19 ms in the IE (n = 7).The ABR interpeak I–V interval was used to determine the neural transmission time between the cochlea and upper brainstem. No statistically significant interaural difference existed in the ABR I–V wave interval . A slight, albeit significant, interaural wave-V latency difference existed for paired comparisons at 70 dB nHL , and at 80 dB nHL , but not at 40, 50 or 60 dB nHL .Not surprisingly, the latency as a function of the stimulus level for waves I, III and V was similar when comparing the NE and IE for all the subjects  , wave-III  and wave I  amplitudes. The effect of the stimulus level was also significant  for wave V, III, and I, respectively. Subject was a significant contributor to the model for wave III (p < 0.001) and I (p < 0.001). Likewise, linear mixed modelling revealed a significant effect of ear (NE vs. IE) on wave V  for wave I, III and V see Seventy percent (14/20) of the subjects underwent MRI of the auditory systems . One subMalformations of the auditory system were identified in 64% (9/14) of the subjects. The prevalence of malformations was higher in children with profound uSNHL, as 86% (6/7) of the children with an ABRthr >90 dB nHL showed malformations, whereas children with mild to profound uSNHL demonstrated a malformation prevalence of 43% 3/7; .n = 7/14; S3, S6, S8, S11–12, S14 and S17), henceforth referred to as cochlear nerve aplasia, although severe hypoplasia cannot be excluded. All cochlear nerve aplasia was combined with hypoplasia of the vestibulocochlear nerve. Six of these seven subjects demonstrated no ABR response , while the ABRthr for S17 was 60 dB nHL . The total percentage of inner ear malformations was 29% , plasma test on the same day as birth (n = 1), or the mother’s lgG and lgM negative CMV blood test shortly after birth (n = 3). The mothers who were CMV lgG and lgM negative left the blood sample for the analysis within 3 months after childbirth (51–88 days).All subjects were CMV negative according to the PCR analysis on the DSP cards typically taken 48 h after birth (n = 19) and 1 mL in the IE . Similarly, the median tympanic peak pressure was 10 daPa in the NE  and 10 daPa and IE . The ears that could not be tested at the research visit  showed normal tympanograms at follow-up visits  in combination with no significant changes in hearing .The change in absolute compliance, measured in equivalent volume of air at tympanic peak pressure was almost identical in the two ears, with medians of 1 mL in the NE , and 95 dB HL in the IEs .An ipsilateral acoustic reflex test was completed in 70% of the infants in the NEs and 70% in the IEs. The median ART was 85 dB HL in the NEs . The mean ± SD response level was 19.8 ± 7.2 dB SPL (n = 18) for NEs, similar to the 19–20 dB SPL in previous research of neonatal NEs with a similar test setup [n = 18), the stimulus stability was high , and a median of 233 sweeps were used . The whole-wave reproducibility was high with a median of 90% , and the median entire SNR was 6.4 dB . The IEs did not pass UNHS and likewise no TEOAEs could be recorded at the research visit .All TEOAE recordings in NEs showed a SNR > 4 dB in at least three of the upper four wide-frequency bands  in 16/17 NEs  and at two frequencies or more for 17/17 NEs .In comparison, a DPOAE response was recorded at three frequencies or more (1–8 kHz) in 5/18 IEs , all with corresponding IE ABRthrs of 35–45 dB nHL (no reliable/no DPOAE recording for S13 and S15) . DPOAE rAlthough DPOAEs were recorded in some IEs, the DPOAE response levels (dB SPL) were generally weaker in the IEs compared to the NEs, as expected. For the frequencies with DPOAEs in the IEs  > 0 dB), the median response level was −0.2 dB SPL (IQR: −3.8 to 6.3 dB SPL), in comparison to 17.7 dB SPL  in the NEs.Infants with mild to profound congenital uSNHL, consecutively recruited from the newborn hearing-screening program, were diagnosed with malformations of the auditory system in 64% of cases 9/14); 86% for congenital SSD (6/7) and 43% for mild to severe congenital uSNHL (3/7). Thus, the diagnostic yield of 64% was numerically somewhat higher than other studies of uSNHL and MRI of 37–58% ,14,18,19; 86% forn = 10) and 75% in preschool children with SSD (n = 20), compared to 48% in children with SSD in general (n = 50) [The most common malformation was cochlear nerve aplasia in 50% of scans 7/14, , which w(n = 50) , indicat(n = 50)  found no(n = 50) ,54, and (n = 50)  with MRIThe 29% inner ear malformations 4/14) were similar in prevalence to the 28–46% in previous studies ,13,14,18 were simAll subjects were cCMV negative. Children with uSNHL has previously been found to be cCMV positive in around 10%  to 20% oDetecting cCMV-associated progressive uSNHL during the first years of life without universal neonatal cCMV screening is a challenge. Clinical protocols for finding these patients needs careful consideration, as they are potential CI candidates ,59,60,61The aim of this study included describing affected mechanisms in congenital uSNHL. We found that the ABR I/O function for the NE and IE were parallel shifted  and inteThe parallel shift in ABR I/O functions was supported by the statistically significant effect of ear and stimulus level on waves I, III and V in the linear mixed model. From studies of adults with cochlear hearing loss and loudness recruitment, ABR amplitudes are expected to be significantly lower near the ABRthr in the IE than at the corresponding stimulus level in the NE, with similar amplitudes in the IE and NE at higher ABR stimulus levels of about 70–80 dB HL  and 60–8The absence of loudness recruitment was also reflected in the ARTs, as a significant interaural difference existed on the group level . This agABR I/O functions in combination with ARTs may be useful clinical tools, especially the ABR, as it is already measured as a first or second step by many UNHS programs, and ABR I/O functions have shown to be similar for wave I and V from birth to adulthood ,68. The The ABR I/O function may add important information to be used in the choice of amplification and compression settings for pediatric patients. Most amplification guidelines for pediatric SNHL recommend the use of validated pediatric-focused prescriptive formulas, i.e., the desired sensation level (DSL) v.5 ,70 or thn = 20) were similar to the median 50 dB nHL ABRthr, the 56% males and 61% left IEs (n = 18) with congenital uSNHL previously screened in the UNHS program in Region Stockholm  [A strength of this diagnostic study is the prospective design of consecutively recruiting all children with congenital uSNHL in Region Stockholm during a two-year period, reducing sample bias. The median 55 dB nHL ABRthr, the 50% males and 65% left IEs n = 0 were sige rate) ,20,21. AVarious recruitment steps were undertaken to invite all children born with uSNHL and excluding all children with temporary hearing loss. However, some children may have been missed in the recruitment process, despite our efforts to differentiate conductive from sensorineural components based on the tympanograms, ARTs, otomicroscopy by an experienced otologist, ABR amplitudes and latencies, and our attempts to reschedule follow-up visits to ensure normal hearing once OME was resolved. Based on earlier screening results in Region Stockholm, we expected about ten more participants , with 51n = 6/7), though considerably high also in ears with mild to severe uSNHL at 43% (n = 3/7). The most common malformation was an absence of a cochlear nerve found in 50% of the MRI scans, followed by 29% inner ear malformations, of which 21% of all MRIs demonstrated EVA. Thus, MRI is powerful in finding possible causes for congenital uSNHL and may be used to find CI candidates with risks of unilateral to bilateral progression . All 20 subjects tested negative for cCMV infection, indicating that it may be relatively uncommon with cCMV infection with very early uSNHL onset, although fluctuations in infection exposure over time should not be overlooked. The parallel shifted IE and NE ABR I/O functions and the interaural ART difference indicate that many children with mild-severe congenital uSNHL may not experience typical loudness recruitment associated with cochlear hearing loss. More research is needed on how supra-threshold measurements, such as the ABR I/O function and the ART, can be used to improve amplification and compression settings in pediatric hearing aids, as poor fittings may contribute to the large variability in hearing aid use and outcomes for children with uSNHL.In this prospective etiology study of infants with congenital uSNHL, 64% of the MRIs revealed abnormal anatomical structures. In ears with a profound degree of uSNHL the malformation incidence was especially high at 86% (


Hearing impairment is prevalent in the general population; early intervention facilitates proper development.To establish the prevalence of hearing impairment in infants at risk, born between June 2006 and July 2008, and to correlate the variables with hearing loss.descriptive and cross-sectional.188 newborns were evaluated using evoked otoacoustic emissions and distortion product and auditory behavior. Tests were repeated if the results were altered. If altered results persisted, the child was referred for impedance testing and, when necessary, for medical evaluation. Infants with normal conduction were referred for brainstem auditory evoked potential testing.Of 188 children two (1.1%) were excluded, and 174 (92.6%) had results within normal limits. Hearing impairment was found in 12 children (6.3%); hearing loss was retrocochlear in three infants (25%). Unilateral hearing loss was present in two infants (16.7%); bilateral hearing loss was present in 10 infants (83.3%).The high prevalence of hearing impairment in this population underlines the importance of early audiological testing. Impaired hearing is prevalent in the world population. Intervening before the age of 6 months allows for normal development of language regardless of the degree of hearing loss.This condition may occur in neonates at or not at risk. The prevalence in low-risk neonates ranges from 0.09 to 2.3%;7The Joint Committee on Infant Hearing (JCIH) has proposed risk indicators to be used internationally,11The purpose of this study was to verify the prevalence of hearing impairment and to correlate it with risk indicators in neonates born and monitored at a tertiary hospital.This descriptive cross-sectional study included neonates weighing 1,500 g or less and a gestational age of not more than 34 weeks, admitted to the neonatal intensive care unit of a reference hospital. After being discharged, these patients were monitored from June 2006 to July 2008. Patients who did not undergo all tests and did not have a final audiological diagnosis during the study period were excluded.A medical history focused on the risk factors proposed by the JCIHA Biologic AUDX 1 device was used for DPOAE testing. Positive results were adequate responses in three of four tested frequencies .Behavioral observation consisted of using non-calibrated instruments (jingle bells and large agogo) to note attention to sounds, exacerbated responses, the cochleopalpebral reflex (CPR), startle, and the habituation phenomenon. Adequate responses were children with the CPR and habituation upon startle.An Interacoustics AZ7 impedance meter was used in immittance testing; a type A tympanometric curve  reference values were applied as normal values for analyzing wave latency and interpeaks, according to the corrected age of each patient.The response variable was the presence of hearing loss; the independent variables were sex, type of delivery, gestational age, the 1 and 5-minute Apgar scores, weight and whether it was appropriate, small or large for the gestational age, a family history of hearing loss in infancy, congenital infection  infection, herpes, and syphilis (TORCH infections), maternal HIV carrier, whether exchange transfusion was made, time in an incubator, and presence and degree of peri-intraventricular hemorrhage, leukomalacia, meningitis, malformation, use of ototoxic drugs, mechanical ventilation, syndromes, use of recreational drugs and/or alcoholic beverages by the mother during pregnancy, and consanguinity of parents.The Epi Info software was applied for calculating the sample. The assumptions were a 95% confidence interval and a 5% margin of error. The estimated hearing loss for similar populations in the literature was 6.3%.Information gathered from the medical history and audiological testing was entered into a database developed in Epi Info version 2001 . The study variables were sex, gestational age, type of delivery, and the presence of risk factors for hearing loss in neonates and lactating infants. Descriptive data resulted from frequencies and percentages of categorical variables, and central tendency measures (mean and median) and measures of dispersion (standard deviation) for quantitative data. The response variable in this study was hearing loss.Data analysis was a two-step process, starting with the univariate analysis. The chi-square test, Fisher's exact test and the odds ratio were applied for comparing proportions. Student's t test was used for comparing the response variable and the categorical covariates when the usual assumptions of the model were met . Otherwise the Mann-Whitney test was applied. The Kolmogorov-Smirnov test was used to check the assumption of normality of the t-test, and the Levene test was applied to check for homocedasticity.Multivariate analysis consisted of a logistics regression model, which initially included all variables with a p-value ≤ 0.25 in the univariate analysis - those at least trending towards statistical significance. Next, a stepwise process was applied until only the statistically significant variables  were included in the model; the clinical relevance was also taken into account. The interactions among all covariates in the final regression model were tested. The software R (public domain) was applied for the multivariate analysis.The institutional review board approved this study (Opinion no. ETIC 271/05). The caretakers of newborn subjects signed a free informed consent form authorizing data gathering.The initial sample comprised 188 children of which the medical and family histories were taken. Two patients (1.1%) were excluded - they undertook hearing screening but not BAEP testing by the end of the data-gathering period, and their evaluation was therefore incomplete. Hearing loss was found in 12 infants (6.3%) of the sample. Unilateral hearing loss was detected in two of these infants (16.7%), and bilateral hearing loss was found in the other 10 (83.3%). Among infants with hearing loss, three (25%) had retrocochlear disorders. These children with hearing loss were referred to otorhinolaryngological care and a speech therapy.The gestational age ranged from 25 to 37 weeks in the 186-subject sample; the median was 31 weeks. The weight ranged from 560 to 2,925 g; the median value was 1,502.5 g. The 1’ Apgar score ranged from 1 to 9 (median - 7) and the 5’ Apgar score ranged from 3 to 10 (median - 9). One infant (0.5%) had congenital syphilis, one infant (0.5%) had congenital toxoplasmosis, and another infant (0.5%) had CMV infection. Five mothers (2.7%) were HIV-positive.Very low birth weight infants tended to have worse results in hearing testing compared to those with higher birth weights. The presence of a family history of hearing loss in infancy increased the chance of an infant presenting hearing loss fivefold; any syndrome also present raised this chance of having hearing loss to 20 times the normal range.This study describes the prevalence of hearing loss and the features of children born in a tertiary reference hospital and monitored in an outpatient clinic for patients discharged from that hospital. The findings confirm the 6.3% prevalence of hearing loss encountered previously in a survey of very low birth weight infants in Brazil using a similar method (DPOAE and BAEP testing).19Other studies of newborn infants in neonatal intensive care units show higher prevalence rates, which may be the result of multiple risk factors for hearing loss in this group.20Variation among studies may be due to other prenatal variables, healthcare, and infections that may cause hearing loss. Other factors are the quality of life of a given population, access to adequate nutrition, and the level of culture.A recent survey in the state of Bahia aimed to investigate the etiology of hearing loss and found that the main cause was rubella of the mother, followed by pyogenic meningitis, idiopathic causes, prematurity, hereditary factors, neonatal jaundice, and others such as chronic otitis media and ototoxicity.Congenital toxoplasmosis, which is frequent in Brazil, may cause hearing loss. It may develop subclinically, compromising the early diagnosis of hearing loss. A recent survey in the city of Belo Horizonte showed that the prevalence of congenital toxoplasmosis is 1 for every 1,590 live births. Patients with this disease were referred for audiological investigation, the results of which showed that 21.1% of these infants had sensorineural hearing loss and 10.5% had conduction hearing loss.Hearing loss in CMV infection is generally progressive. The infant with CMV infection in this study acquired the disease after a blood transfusion; statistical significance, however, was not attained. This is probably because the sample of mothers with prenatal CMV serology is low (only 44 of 186 took this test), resulting in a lesser effect on the data. Additionally, the first signs of hearing loss may present late; thus, a study monitoring the development of hearing and language in children may show a higher prevalence of hearing loss caused by CMV infection.A systematic review of studies on congenital CMV infection revealed that if the prevalence at birth is 0.7% and the risk of bilateral moderate to profound sensorineural hearing loss is 3 to 5%, the risk of a child developing permanent bilateral hearing loss because of CMV infection is 0.21 to 0.35 per 1,000 births.Our study showed a statistically significant difference in infants of HIV-positive mothers. However, another study of hearing in infants of HIV-positive mothers compared with those of HIV-negative mothers concluded that the risk of sensorineural hearing loss was not higher in the former group.Other authors have suggested that AIDS should be considered a risk factor for peripheral and/or central hearing loss.The study method included DPOAE testing in two or three steps, and immittance and BAEP tests . A recent study of 4,519 infants aged not more than 3 years concluded that DPOAE testing (using the same equipment and protocol of the present study) in several steps and monitoring guidelines are useful for detecting hearing loss.This study started in 2006; at that point, the most recent JCIH recommendations were those of 2000. For completeness, our study included the JCIH indicators of the years 1994 and 2000. New JCIH recommendations were published on October 2007; these guidelines emphasized that high-risk children should be evaluated using BAEP testing because of the risk of auditory neuropathy.This method enabled the detection of three cases of retrocochlear disorders in the study sample, thereby underlining the concern with such conditions in infants with risk factors. The prevalence of these disorders in children with profound hearing loss was 0.94%;Monitoring of children aged up to 2 years may also reveal cases of progressive or delayed onset hearing loss, given that the study sample consisted of high-risk infants for all types of hearing loss.This study aimed to detect the prevalence of auditory disorders in children exposed to several risk factors, because it is thought that the prevalence of hearing loss is high in this population group. In these subjects, multiple factors may result in progressive or delayed onset neonatal or postnatal hearing loss, which should be assessed and monitored in a hearing screening program.Timely diagnosis and interventions for speech development are not the reality throughout Brazil in most cases of prelingual hearing loss. The population and healthcare professionals involved in childcare should be made aware of the impact of hearing loss; this could result in increased adhesion to neonatal screening programs.


Development and validation of the protocol for the evaluation of voice in patients with hearing impairment (PEV-SHI)”, published in Braz J Otorhinolaryngol. 2020;86:748-62, with DOI number https://doi.org/10.1016/j.bjorl.2019.05.007, in the title of the article, where it reads:In the article “Development and validation of the protocol for the evaluation of voice in patients with hearing impairment (PEV-SHI)It should read:Development and validation of the protocol for the evaluation of voice in subjects with hearing impairment (PEV-SHI)


This article presents high-resolution swept-source optical coherence tomography (SS-OCT) imaging data used to elaborate a mechanical model that elucidates the formation of outer retinal corrugations (ORCs) in rhegmatogenous retinal detachments (RRD). The imaging data shared in the repository and presented in this article is related to the research paper entitled “Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory” . The dataset consists of 69 baseline cross-sectional SS-OCT scans from 66 patients that were assessed for the presence of ORCs and analyzed considering the clinical features of each case. From the 66 cases, we selected SS-OCT images of 4 RRD patients with visible ORCs and no cystoid macular edema (CME) to validate the mechanical model. We modelled the retina as a composite material consisting of the outer retinal layer (photoreceptor layer) and the inner retinal layer (the part of the retina that excludes the photoreceptor layer) with thicknesses  Specifications TableValue of the Data•Following rhegmatogenous retinal detachment there are several structural changes that occur to the retina, which can subsequently result in post-operative anatomic abnormalities and worse functional outcomes. This dataset helps us understand what happens to the mechanical properties of the retina that result in the occurrence of outer retinal corrugations.•Professionals in Ophthalmology/Retina and engineers could use this imaging dataset and corresponding data/mechanical models to study other conformational changes that occur in the structure of the retina in the setting of rhegmatogenous retinal detachment.•Outer retinal corrugations (ORCs) that do not resolve result in outer retinal folds and worse functional outcomes. Thus, understanding the pathogenesis of ORCs may lead to modifications in retinal detachment repair concepts and techniques that favor the resolution of ORCs prior to contact of the retina with the retinal pigment epithelium.1i and Eo, respectively) and the necessary energy that would be required to bend the tissue with the observed frequencies.This imaging dataset is related to an original research article  2These imaging data consist of real-time Swept-Source Optical Coherence Tomography (SS-OCT) scans that demonstrate morphological characteristics of retinal detachments with and without outer retinal corrugations (ORCs). The ORCs observed in these SS-OCT images are a visual representation of RPE-photoreceptor dysregulation in patients with extensive and progressive detachments, a concept described in the original research article  3in vivo with the assistance of SS-OCT.This was a prospective cohort study of patients with primary rhegmatogenous retinal detachment (RRD) who presented to the tertiary vitreoretinal surgery practice at St. Michael's Hospital, Unity Health, Toronto, Ontario, Canada from August 2020 to February 2022. To assess the occurrence of outer retinal corrugations (ORCs), baseline imaging was performed in every patient as described by Muni et al. 66 cross-sectional OCT scans were assessed for the presence of ORCs and analyzed considering the clinical features of each case, to determine the presence of RPE-photoreceptor dysregulation. From the 66 cases, a sub-set of SS-OCT images was used to deduce the mechanical properties that are likely to lead to conformational changes in the retina upon detachment. ORC mathematical models are explained in detail below:Ultra-widefield fundus imaging shows that the retina typically exhibits full-thickness undulations, where the outer and inner retina deform symmetrically. To understand this, recall that the healthy retina is affixed to the retinal pigment epithelium (RPE), which is a nearly spherical surface of radius, say For detachments with heights greater than the critical height  in the outer retina are superimposed on the long wavelength undulations of the full-thickness retina. This suggests that the pathophysiology of ORCs could involve processes that result from differences in the mechanical properties of the outer and inner retina in RRD. To estimate the difference in Young's elastic moduli of the outer and inner retina in the detached state  of bending modulus Assuming a sinusoidal form for the perturbation in the shape, Rendering the equations dimensionless, we deriveHere,The parameter To find the optimum value of Ethics Committee approval was obtained from St. Michael's Hospital/Unity Health Toronto (REB 18-018), all participants underwent informed consent by the research coordinator, and the study was carried out in accordance with the Declaration of Helsinki.Isabela Martins Melo: Methodology, Writing – original draft, Writing – review & editing. Masoud Nourouzi Darabad: Methodology, Software, Validation, Writing – original draft. Arun Ramachandran: Conceptualization, Methodology, Software, Validation. Paola Lourdes Oquendo: Data curation, Methodology. Hesham Hamli: Data curation, Methodology. Wei Wei Lee: Data curation, Methodology. Flavia Nagel: Data curation, Methodology. Aditya Bansal: Data curation, Methodology. Rajeev H. Muni: Investigation, Conceptualization, Writing – original draft, Writing – review & editing, Supervision.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Ryan’s Retina edited by Steven Ryan is a successful example of multilateralism. This is the 7th and latest edition of Ryan’s standard work “Retina” from Elsevier Publishers and is now available in bookstores.Anyone who thinks of ophthalmology as a minor matter will be enlightened by the three volumes on the retina alone. Srinvas Sadda, who succeeded the late Steve Ryan as head of Doheny’s Eye Foundation, has also accepted the editorship of “Retina.” This continues Steve Ryan’s vision of global openness, curiosity, and nurturing.Authors and co-editors from America, Europe, Asia, Australia, and China have contributed to this current edition, which should be read by ophthalmic residents, in order to assist in giving them an overview. “Retina” is also suitable for working in basic research on the retina. However, most often, practicing ophthalmologists will use it as a reference. The main benefit from the focus of the opinion leaders in our field, for example, is when weighing up competing therapy methods. Ryan’s Retina renews itself with each edition.Finally, artificial intelligence and the problem of segmentation in automated imaging are considered. The practicing retinologist is regularly confronted with symptoms from border areas, not only with internal medicine but also with neuro-ophthalmological differential diagnoses. In an overlapping area, symptoms can originate not only from the retina but also from superordinate central nervous structures. I would recommend a future edition to include a chapter that leads from symptom to diagnosis, such as phosphenes, glare, flare, palinopsia, and visual snow.Ryan’s Retina makes it easier for residents and practicing ophthalmologists to work on patients and for basic researchers to familiarize themselves with retina. We can only thank the authors, the editor in chief, and the co-editors for their self-sacrificing work. I will certainly use the digital version of Ryan’s Retina more often, due to access from anywhere via PC/laptop.Also, in this 7th edition,


Osteoporosis is a common disease of old age. However, in many cases, it can be very well prevented and counteracted with physical activity, especially high-impact exercises. Wearables have the potential to provide data that can help with continuous monitoring of patients during therapy phases or preventive exercise programs in everyday life. This study aimed to determine the accuracy and reliability of measured acceleration data at different body positions compared to accelerations at the pelvis during different jumping exercises. Accelerations at the hips have been investigated in previous studies with regard to osteoporosis prevention. Data were collected using an IMU-based motion capture system (Xsens) consisting of 17 sensors. Forty-nine subjects were included in this study. The analysis shows the correlation between impacts and the corresponding drop height, which are dependent on the respective exercise. Very high correlations (0.83–0.94) were found between accelerations at the pelvis and the other measured segments at the upper body. The foot sensors provided very weak correlations (0.20–0.27). Accelerations measured at the pelvis during jumping exercises can be tracked very well on the upper body and upper extremities, including locations where smart devices are typically worn, which gives possibilities for remote and continuous monitoring of programs. The prevalence of osteoporosis has increased significantly in recent years. Worldwide, about 33% of women and 20% of men over age 50 will experience osteoporosis fractures ,2. The fHigh-impact exercises  have been shown to affect bone mineral density (BMD), especially of the femur in premenopausal (age 35–40 years) women ,17. To vA positive effect between jumping exercises and osteoporosis has been demonstrated, with the underlying kinematics and possibilities to track those in a natural setting still being interesting topics. Thus, our conducted study combines two parts to further investigate this topic—a rather mechanical/theoretical part to validate the effectiveness of different body parts to measure and identify those jumping exercises and secondly, a more in-depth analysis of the kinematic and preventive aspects focusing on osteoporosis. The presented manuscript focuses only on the first topic.Single acceleration data or the combination of acceleration data measured at different points allow drawing conclusions about certain movements and their effects on the body. This study aims to evaluate acceleration curves of different body segments during high-impact exercises (jumps) to understand the kinematics behind the positive effects of jumping exercises on osteoporosis.The intention is further to clarify at which segments or body regions jumping-exercise-based impacts on the lower extremities can best be recorded compared to findings on hip worn measurements. Can these loads be tracked at the locations where smart devices are typically worn, such as the wrist (smartwatch), upper leg (smartphone), or sternum (chest strap), which are more pleasant and more manageable in everyday life?Forty-nine participants were recruited for this study. All of them granted informed consent. BMD peaks at around age 30. Women lose BMD faster than men. After menopause, the risk of developing osteoporosis increases in women. The age ranges were chosen to include subjects in whom BMD tends to begin to decline, but women have not yet reached menopause. The upper age limit was standardized for all genders ,23. TherThe jumping exercises were recorded at 60 Hz using 17 IMUs  for a full-body setup, comprising a 3-axial accelerometer, gyroscope, and magnetometer. The sensors were placed on the head, shoulders, upper sternum, pelvis, upper and lower legs, and feet with Velcro straps. Besides the motion capture data generated via sensor fusion algorithms, specific parameters, like acceleration or orientation, can be analyzed separately to imitate smart devices worn on the body. A 30 cm-high wooden box served as a raise to perform the drop jumps. The height was chosen to give the subjects a safe feeling when performing the exercise. Due to the different physical activities performed in their free time, some subjects were less familiar with jumping exercises. The aim was to keep the risk of injury low and still maintain a high impact on the bones. Previous studies suggest not going higher than 30 cm ,25.The procedure of the experiment was explained to the participants, and their consent was obtained before recording. Demographic and anthropometric data of the subjects, such as age, gender, weight, height, were collected, as well as physically active time and previous musculoskeletal injuries in the last two years. The subjects performed different jumping tasks five times each, containing Squad Jumps (SJ), Countermovement Jumps (CMJ), and Drop Jumps (DJ). The exact execution of the exercises is shown in Before every exercise, the right execution was demonstrated, and the subjects were allowed to do a test run first to get used to the task and the system. The subjects had to keep their hands on their hips during the exercises. If the execution was not done right, the subjects were asked to repeat the trial.Motion capture data from Xsens were reprocessed by MVN Analyze software  (MVNA). Further data processing and analysis were performed using Python  with the packages numpy (v. 1.18.5), pandas (v. 1.0.5), seaborn (v. 0.10.1), and scipy (v. 1.7.2). Acceleration values in gravitational direction for all 17 IMUs, were extracted from the MVNA post-processed files for all subjects (49), exercises (3), and trials (5). Only accelerations in gravitational direction were considered, as the impacts of the jumping exercises affect the body in the gravitational direction. The execution of the jumps takes place without significant movements in the transverse plane. In the first step, the measurement data were cut down to the period of the actual exercise. Subsequently, trajectories of the acceleration graphs between the different sensors and the three jumping exercises were compared according to the highest accelerations, as these maxima can be equated with a high impact on the body or bone. The maximum jump height for each trial was evaluated using MVNA software.In the further course, the jumping exercises were considered and evaluated separately. The Pearson correlation coefficients ρ were calculated for each possible combination of the time series of the pelvis sensor and the 16 other sensors for each subject and trial. As correlation coefficients are not unbiased, the average of several correlations will not converge to the true correlation. Therefore, the correlation coefficients are transformed with the Fisher z-transformation, then averaged, and finally, calculated back into the Pearson correlation coefficient. The Pearson correlation coefficients were interpreted according to Cohen (1988), where ρ ≤ 0.29 should be considered as low correlation, 0.30 ≤ ρ ≤ 0.49 as moderate correlation, and 0.50 ≤ ρ as strong correlation .The graphs of the acceleration in gravitational direction show very similar curves for all sensors. Positive accelerations in the graphs spatially mean a movement upwards (jump) or the deceleration of the movement at the landing. Clear outliers can only be observed for the accelerations of the foot sensors. The peak accelerations here are partly two times that of the remaining sensors. For the DJ, however, the differences are smaller. In order to illustrate what has been described, the graphs of the accelerations for one randomly selected person are shown in Comparing the maximum accelerations of the sensors for each exercise, the medians for DJ are higher than for SJ and CMJ. The second-highest accelerations occurred for CMJ. The comparison of the sensors for the exercises is shown in The evaluation of the drop height shows, on average, 0.37 ± 0.06 m  for the SJ and 0.41 ± 0.07 m  for the CMJ. For these two jumps, the maximum jump height is evaluated, which results in the drop height. This is achieved by the subject’s jumping power. For the DJ the average maximum drop height of 0.47 ± 0.02 m  corresponds to the height after jumping off the 30 cm high box and not after the bouncing hop.Pearson’s correlation matrix over the whole time series shows that the measured accelerations in the direction of gravity correlate very well for all exercises between the pelvis sensor and sensors at the upper body. Here, all correlation coefficients are above 0.87 . For the thighs, the correlation with the pelvis sensor is still above 0.83 . Accelerations in the lower leg correlate less well with the pelvis. The coefficients here take values between 0.66 and 0.74. The foot sensors do not correlate with the upper body with values below 0.27 . A heat map pointing out the correlation strengths is shown in In this study, acceleration data from 17 IMUs recorded during three different jumping exercises were analyzed and evaluated. The results show that the maximum accelerations experienced by the body or the individual body segments depend on the jumping exercise performed. The DJ exerts the highest accelerations on the body. The lowest impacts are achieved by the SJ. This gradation can be attributed to the different drop heights, which are the highest for the DJ. Another reason for the increased accelerations over the entire body could be the bounce hop, in which the impact is mainly absorbed by the ankle joint. The knee does not flex as much here as it does in the other two exercises. The high accelerations in the foot sensors can be explained by the kinematic chain. The feet are the first segments of the body to be decelerated when landing. All other segments are cushioned distally via the intermediate joints  and the muscles running above them. They are also very unstable until they finally come to rest flat on the ground. The strong deviations in the curve to the other sensors can be attributed to this.These deviations can also be seen in the correlation coefficient matrices shown in The maximum accelerations at the different sensor positions indicate that the impact of the jumping exercises can be measured with an acceptable accuracy on almost all parts of the body. When these results are compared with previous studies, the mean values tend to be lower in the present study. This can be attributed to the lower sampling rate, which has the disadvantage that very short acceleration peaks may not be detected. Vainionpää et al. (2006) used an IMU with a sampling rate of 400 Hz . The accThis study compares different jumping exercises whose execution is predetermined. Therefore, the results cannot be generalized. Other movements or movement patterns must be evaluated separately, as the extremities experience different accelerations during other movements. In addition, the Xsens sensors cannot be accurately compared to smart devices, even if the placement can be assumed to be the same. In this study, the sensors were fixed to the skin with Velcro straps. A consistent position of the sensor is important, as can be assumed with a smartwatch, for example. Smartphones, on the other hand, are not so well suited, as they have degrees of freedom in the trouser pocket, which can lead to wrong results. Specifications of wearables must be observed before use. They must be able to record the same parameters, and these parameters should also be retrievable to evaluate the performed exercises.The characteristics of the test persons were very different in this study. Especially the different physical conditions and training levels should be emphasized, which made a controlled execution of the exercises difficult due to a lack of coordination and jumping power. Having this wide range of subjects reinforces the high correlations. Nevertheless, it leaves room to examine the results in detail under the aspects of age, gender, and weight in order to be able to make even more specific statements.The study shows that the accelerations measured at the pelvis during jumping exercises can be tracked very well on the upper body and upper extremities. It sets a basis regarding the kinematic relationships of different body segments during these jumping exercises. This includes the locations where smart wearable devices are typically worn, such as the wrist (smartwatch) or sternum (chest strap). Sensors positioned at the thighs do not offer as good correlations as the upper body and extremities but are still strong. If attention is paid to the correct execution of the exercise, the sensor placement is almost arbitrarily variable. These results suggest that these jumping exercises can be used in possible wearable app combinations to assist with the execution and provide important information regarding impact. As shown in past studies, these jumping exercises are sufficient to have a positive effect on BMD. The impact forces and the exact preventive kinetic mechanisms regarding osteoporosis are difficult to deduce from the accelerations measured at the upper body. Therefore, possible further kinematic and kinetic correlations are to be clarified in future investigations.


Auditory neuropathy spectrum disorder (ANSD) is characterized by impairment of the auditory nerve associated with preservation of outer hair cell function.To establish the prevalence of ANSD in subjects with sensorineural hearing loss (SNHL).This retrospective study was carried out between 2010 and 2012 and included the charts of 2,292 individuals with SNHL. Data from otolaryngological and audiological examinations based on pure-tone and speech audiometry, impedance tests, otoacoustic emissions (OAEs), and brainstem auditory evoked potentials (BAEPs) were collected. Inclusion criteria: presence of OAEs and/or cochlear microphonic (CM); absent or altered BAEPs, and normal MRI scans of the brain.Twenty-seven (1.2%) of the 2,292 subjects with SNHL had ANSD . Mild SNHL was seen in 29.6% of the individuals with ANSD; 55.5% had moderate SNHL; 7.4% had severe SNHL; and 7.5% had profound SNHL. In terms of age, 14.8% were aged between zero and 20 years, 44.1% were 41 to 60 years old, and 7.4% were above the age of 60.ANSD was seen in 1.2% of the individuals with SNHL included in this study. The term auditory neuropathy has been used to describe diseases affecting children and adults characterized by normal outer hair cell function and anomalous or absent auditory nerve function; it has been described as a set of auditory disorders that combine otoacoustic emissions (OAEs) and/or cochlear microphonics (CM) with absent or desynchronous waves generated in brainstem auditory evoked potentials (BAEPs). The term auditory neuropathy was used for the first time in a study carried out in 1996 to categorize a group of subjects with hearing symptoms and normal cochlear function associated with cochlear nerve dysfunctionThe term auditory neuropathy spectrum was produced through international consensus during the Guidelines Development Conference on the Identification and Management of Infants with Auditory Neuropathy, held in June of 2008Individuals with auditory neuropathy spectrum disorder (ANSD) may present mild to severe, unilateral or bilateral hearing loss associated with disproportional impairment of speech discrimination in relation to hearing lossThe published estimated prevalence rates of ANSDThe site of injury in ANSD patients has not been clearly defined. Investigated sites include the inner hair cells, the synapses between inner hair cells and the auditory nerve, dendrites or neural axons, afferent and efferent activity of the auditory nerve, spiral ganglion neurons, and neurotransmitter biochemical anomaliesThis study aimed to identify the prevalence of ANSD in a group of individuals with sensorineural hearing loss seen at an auditory health care center.This cross-sectional historical cohort study was approved by the Research Ethics Committee of the institution (permit #190.328).•SNHL;•Ear endoscopic examination characterizing normal middle ear function;•Transient otoacoustic emissions and/or cochlear microphonics in brainstem auditory evoked potential testing;•Absent acoustic reflex;•Absence of waves on BAEP testing or waves with severely altered morphology;•Brain MRI scans ruling out retrocochlear diseases that could affect BAEP responses; MRI scans were made in other centers, therefore the reports were used to exclude patients only.The study included subjects diagnosed with sensorineural hearing loss (SNHL) seen in an audiological care center from 2010 to 2012. The enrollment criteria included:•Individuals with mixed or conductive hearing loss according to pure-tone and speech audiometry;•Individuals not willing to cooperate during tests;•Subjects with retrocochlear disease seen on MRI scans.Exclusion criteria:A total of 2,292 individuals diagnosed with sensorineural hearing loss with ages ranging from zero to 95 years were assessed. They underwent thorough assessment, comprised by ENT examination to find the status of the ear canal and the tympanic membrane through conventional otoscopy; basic audiological examination including impedance tests, pure-tone audiometry, and speech audiometry. The following devices were used: impedance testing device AT-235 (Interacoustics), audiometer AC-33 (Interacoustics).OAEs were recorded with a Madsen Capela (Otometrics) device. Distortion product otoacoustic emissions were recorded at 700 Hz and 8000 Hz, and intensity of stimuli was kept fixed on L1 at 65 dBNPS and L2 at 55 dBNPS along with a ratio between frequencies of 1.22 (F2/F1 = 1.22). Response was interpreted as present in the frequencies in which the signal to noise ratio was 6 dB, reproducibility was equal to or greater than 70%, and stability was equal to or greater than 75%.BAEPs and CM were assessed using device Chartr EP (Otometrics) with patients wearing in-ear earphones. Monaural clicks set initially at 100 dBNA were used at least twice in BAEP testing to confirm the presence of overlapping waves. Stimulus frequencies ranged from 250 Hz to 8000 Hz each lasting 100 microseconds; condensation and rarefaction clicks were presented 27.7 times per second with a 12 ms window. Absence of wave formation on BAEP testing with stimuli up to 100 dBNA and severe wave morphology alterations in BAEP consisting of low amplitude wave V at 100 dBNA were characterized. CM was recorded during BAEP testing using clicks with inverted polarity (condensation and rarefaction). When CM was present at 100 dBNA, intensities in decreasing steps of 20 dBNA were tested to the minimum level at which the potential could be verified. The absolute latencies for waves I, III, and V were measured and found to have varied significantly due to alterations in morphology, amplitude, and latency, but such measurements were not part of the goals of the study. BAEP and OAE tests were conducted without the use of sedatives. The classification proposed by GoodmanTwenty-seven (1.2%) of the 2,292 subjects included in the study diagnosed with SNHL  met the Ten (37%) of the 27 subjects were males and 17 (63%) were females .Graph 2GWhen age distribution was considered, four (14.8%) subjects were aged between zero and 20 years; nine (33.4%) were aged between 21 and 40; 12 (44.4%) were aged between 41 and 60; and two (7.4%) were above 60 .Graph 3APure-tone and speech audiometry indicated that eight (29.6%) subjects had mild SNHL; 15 (55.5%) had moderate SNHL; two (7.4%) had severe SNHL; and two (7.5%) had profound SNHL . ImpedanThe 27 subjects diagnosed with ANSD were fitted with hearing aids. Functional gain was observed in three (11.1%) individuals, and 24 (88.9%) had no functional gain .Graph 5PAuditory neuropathy spectrum disorder is a condition found in patients of all ages with normal outer hair cell function and altered neural functionCochlear microphonics can be assessed through BAEPs or electrocochleography in the diagnostic tests for ANSD. Studies on subjects with ANSD looked into the use of extratympanic electrocochleography (Et-Ecog) and BAEP testing in the differential diagnosis of ANSD, and concluded that Et-Ecog allows for more detailed analysis of cochlear function than BAEPsANSD is a relatively new clinical entity and there still is little evidence on its incidence, prevalence, natural history, and possible courses of therapyThe prevalence of ANSD in subjects with SNHL in our study was 1.2%. The literature contains reported prevalences ranging from 0.5% and 15% in subjects with SNHLStudies carried out with adults showed lower prevalences of ANSD. Lofti & MehrkianPatients of all age ranges were found to have ANSD in this study, but adults accounted for most of the cases, with 23 of the 27 individuals diagnosed with ANSD.ANSD progression and the damage to hair cells caused by the cochlear damage produced by the amplification provided by hearing aids in subjects with SNHL lead to the disappearance of OAEs and hamper the diagnosis of ANSD. Thus, cochlear microphonics become a relevant part of the tests used to diagnose patients with ANSDIn our study, all subjects diagnosed with ANSD met the criteria for preserved cochlear function associated with altered or absent auditory nerve function according to OAE and BAEP testing, respectively. Test results were consistent with the findings described in the literature in regards to gender distribution, age range, and degree of hearing lossCochlear implants may improve the waves on BAEP testing and the speech of subjects with ANSDANSD is not an extremely rare auditory condition. The accurate diagnosis of this disease requires, in addition to audiological assessment, objective OAE, CM, and BAEP tests, as the presence of CM or OAEs associated with BAEP wave absence or dyssynchrony is a significant diagnostic criterion.ANSD is a challenging condition, as many factors concerned with its pathogenesis and etiology are yet unclear. More studies are required to provide much needed clarification on ANSD.The prevalence of auditory neuropathy spectrum disorder in this study in subjects with sensorineural hearing loss was 1.2%, as also reported in the literature.


Gene technology regulators receive applications seeking permission for the environmental release of genetically modified (GM) plants, many of which possess beneficial traits such as improved production, enhanced nutrition and resistance to drought, pests and diseases. The regulators must assess the risks to human and animal health and to the environment from releasing these GM plants. One such consideration, of many, is the likelihood and potential consequence of the introduced or modified DNA being transferred to other organisms, including people. While such gene transfer is most likely to occur to sexually compatible relatives , horizontal gene transfer (HGT), which is the acquisition of genetic material that has not been inherited from a parent, is also a possibility considered during these assessments. Advances in HGT detection, aided by next generation sequencing, have demonstrated that HGT occurrence may have been previously underestimated. In this review, we provide updated evidence on the likelihood, factors and the barriers for the introduced or modified DNA in GM plants to be horizontally transferred into a variety of recipients. We present the legislation and frameworks the Australian Gene Technology Regulator adheres to with respect to the consideration of risks posed by HGT. Such a perspective may generally be applicable to regulators in other jurisdictions as well as to commercial and research organisations who develop GM plants. Horizontal or lateral gene transfer (HGT) is the stable and heritable acquisition by an organism, of genetic material that did not originate from a parental donor . Any DNAvia HGT also needs to be considered as part of the risk assessment.In Australia, the Gene Technology Regulator (the Regulator) receives applications for the intentional environmental release of GM plants and, as part of the assessment process of these applications, must consider the risks to human and animal health and to the environment from gene technology posed by the proposed activities. GM plants may have genetic elements sourced from other organisms imparting desired traits, e.g., increased nutritional value; drought, pest and disease resistance; or increased productivity. While gene transfer is most likely to occur to sexually compatible relatives through vertical gene transfer, the likelihood of gene transfer to non-sexually compatible organisms .” In the United Kingdom, the independent Advisory Committee of Releases into the Environment (ACRE) also considers HGT in their assessment for application for the release of genetically modified organisms (GMOs)  503/2013 of 3 April 2013  states that “The applicant shall assess the probability of horizontal gene transfer from the product to humans, animals and microorganisms and any potential associated risk when intact and functional nucleic acid(s) remains in the genetically modified food and feeds (GMOs) . Other rIn Australia, Regulations 9A and 10 of the Gene Technology Regulations 2001  specify Gene Technology Act 2000 and Regulations, outlines the approach that the Regulator takes to conduct the risk assessment of proposed activities with a GMO. Such activities include the proposed environmental release of the GMO. The RAF describes the three essential components needed for a scenario (set of circumstances) that might give rise to harm as a result of activities conducted with the GMO. The three components are: 1) a source of potential harm, which may be a new or altered property/trait of the GMO; 2) a potential harm to people or the environment; and 3) a plausible causal linkage between components 1) and 2). If a plausible causal linkage or potential harm cannot be described, then the source of potential harm poses no risk  , in acco no risk .While HGT per se is not considered a risk, it fits into the pathway component of risk as it can link the introduced or modified DNA to a potential harm to people or the environment. Therefore, the likelihood of HGT occurring determines the potential for any harm. As the number of steps in a pathway leading to harm increases, the likelihood of harm occurring decreases. The Regulator considers the likelihood of occurrence of HGT and the severity of adverse outcomes if HGT was successful. If the level of risk is increased compared to the status quo, then the Regulator may include specific risk management measures to interrupt steps in a pathway and reduce the likelihood of harm occurring or refuse to approve the proposed intentional environmental release. For example, as a measure to limit the likelihood of gene flow by vertical gene transfer from GM plants, an exclusion zone can be imposed where sexually compatible plants are not permitted to be grown.It should also be noted that risk analysis on a proposal for the release of GM plants occurs in the context of the receiving environment. For example, if a GM (transgenic) DNA sequence was sourced from a ubiquitous bacteria or fungi, then this forms part of the context as the DNA sequence is already in the environment. If HGT from the bacteria or fungi is more likely than HGT from the proposed activities with the GM plant, then the potential of HGT resulting in harm from the release of the GM plant can be no greater than the risk from the parent organism. Similarly, the likelihood of harm occurring as a result of the GM plant release is compared to that of harm occurring in the absence of the genetic modification, i.e., the non-GM plant.Until recently, comparative analysis for detection of HGT events relied on very limited databases of manually annotated genes . HoweverTetranychus urticae) genome, seven years after HGT was first analysed in this species  and Roundup Ready™ canola (MON-ØØØ73-7) possess approximately 8.0 kb and 5.05 kb of transgenic DNA in a genome of approximately 2.75 and 1.13 Gb, respectively . Thus, t® Duracade™ 5222 corn® III × Roundup Ready™ Flex™ cotton (SYN-IR1Ø2-7 × MON-15985-7 × MON-88913-8 × MON 887Ø1-3) possess approximately 40 kb and 30 kb of transgenic DNA, respectively  plants deliberately release extracellular DNA, e.g. from their root tips as a defence strategy against soil microbial pathogens ; and/or The integrity of naked DNA depends on many biotic and abiotic factors  and mostaadA, which is commonly found in soil bacteria was inserted into the DNA of chloroplasts , allowing the natural transfer and integration of part of its DNA, known as transfer-DNA, or T-DNA to the plant genome   . In a prM plants . Howeverromosome  or on moromosome , which iTransformation provides another mechanism for HGT, whereby naked DNA is “taken up” from the environment by naturally competent cells, which are predominantly bacteria . It has via HGT, and this process is mediated through phages  are phage-like particles, found in bacteria and archaea, that can randomly incorporate a piece of the donor’s host genome for delivery upon cell lysis to other nearby recipient hosts and as such, can also facilitate HGT . However–23 per cell. This frequency, as expected, increases if short homologous DNA sequences are present between the donor  and recipient bacteria (7 × 10–13 per cell), but it is still a few orders of magnitude (1014) lower to the naturally occurring rates of HGT between bacteria in the environment (10–1 to 10–8 per cell)  .cry genes from Bacillus thuringiensis imparting insect resistance  as a marker. The analysis showed that the presence of GM grapevine did not increase the level of nptII-resistant bacteria in the soil, as similar levels of naturally nptII-resistant bacteria were found in soil planted with non-GM grapevine  originating from GM corn (event MON-ØØ863-5) and purified plasmid DNA, both containing the aked DNA . The resn 4 days , indicatn 4 days . Thus, mn 4 days .In their diets, humans and animals are regularly exposed to DNA from a variety of sources, including from plants, animals and microorganisms. There are several factors that detrimentally affect the integrity and availability of DNA. These include the process of food preparation, cooking, and digestion of DNA in the GIT, all of which fragment the DNA  and insect resistant corn (event MON-ØØ81Ø-6) were used in feeding experiments that were carried out over ten generations on Japanese quails. The results showed no signs of GM DNA in tissue samples, including the breast muscle, eggs and internal organs  requires additional analysis  strain F13 (F13-cp) to confer resistance against the virus as well as the nptII marker gene as previously discussed. For the viral transgene, analysis of the GFLV population showed a large number of natural recombination events within the virus; however, none of these recombinants contained the F13-cp or nptII transgene sequence (An planting . The grasequence .Cucumber necrosis virus (CNV), which is a positive-sense, single-stranded RNA virus. When Nicotiana benthamiana leaves were infiltrated with the transcript of CNV coat protein, virus-like particles were produced that carried a variety of host RNAs, including retrotransposons and chloroplast-specific RNAs (via the virus to new hosts (Beet curly top Iran virus (BCTIV), a single-stranded DNA virus, can incorporate DNA from its sugar beet host to form hybrid virus-plant minicircles. These can then be packaged and have been shown to replicate and be transcribed in other plant species sensitive to BCTIV infection  have adopted the classification of these genes into three risk groups. These groups class antibiotic resistance genes based on their abundance in the environment and their significance to human and veterinary medicine, reviewed in HGT is most prominent in prokaryotes, as many lack sexual recombination and thus employ HGT as a mechanism for adaptation to the environment. For example, the beneficial acquisition of antibiotic resistance through HGT in a clinical setting, and several other cases of HGT have been researched and documented in this context. Despite the significant role that HGT has played in the evolution of eukaryotic genomes, nuclear HGT events between multicellular eukaryotes are considered scarce, when compared to those between prokaryotes and in either direction between prokaryotes and eukaryotes . SpecifiOverall, the frequency of HGT for all organisms, including viruses and bacteria, is orders of magnitude lower than gene transfer by sexual or asexual reproduction. This is due to HGT needing to overcome numerous barriers, such as those related to the transfer, incorporation, and transmission of the DNA between organisms. In eukaryotes, additional barriers are needed to be overcome, where the DNA may first need to be transferred from the somatic to germ cell line and then be transferred to the recipient’s offspring.N. benthamiana, are likely to be genetically modified with DNA sequences encoding components for production of pharmaceuticals and vaccines (via Site Directed Nucleases (SDN) without guide RNAs (SDN-1) are organisms that are not genetically modified organisms under Schedule 1 of the Gene Technology Regulations 2001 for regulatory purposes following the changes made to the Australian Regulations in 2019 (The advances in whole genome sequencing and comparative genomics demonstrates that, although historical, HGT events in eukaryotic organisms may have previously been underestimated. . Howevervaccines . The DNAvaccines  would st in 2019 .


Evidence on the effects of Acute Care for Elders (ACE) units in frail older adults remains limited. Therefore, we aimed to evaluate the effects of the ACE unit on functional outcomes in frail older adults.n = 28), prefrail , and frail . The primary outcome was the activities of daily living (ADL) measured by the Barthel Index at admission and before discharge. Paired sample t-test was employed to determine the difference in ADL. Multiple linear regression analysis, with adjustment for covariates, was conducted to examine the association between frailty status and change in ADL.In this prospective observational study, we enrolled 114 consecutive patients aged 65 years and older admitted to the ACE unit for acute medical conditions between October 2019 and September 2020. The FRAIL scale  was used to classify the patients into three groups: robust . After covariates adjustment, a significant association between frailty status and change in ADL was found .Among 114 patients enrolled , 77 (67.5%) were female. ADL at admission (60.3 ± 31.9) and before discharge (83.7 ± 21.6) were significantly different (Older adults with frailty experienced functional improvement after admission to the ACE unit. Prefrail and frail groups were associated with a more significant change in ADL between admission and discharge compared to the robust group. Frailty is a common and important geriatric syndrome associated with adverse outcomes, including hospitalization, disability, and mortality –4. The pAcute Care for Elders (ACE) units are currently one of the strongest evidence that redesigned age-friendly care systems could improve functional outcomes and increase the likelihood of discharge to home –11. ACE The effect of functional disabilities recovery in relation to frailty status in geriatric care units remained undermined. One retrospective observational study in an acute geriatric ward showed that an increasing frailty status may be related to a lower functional recovery ; howeverIn this prospective observational study, patients from the acute geriatric ward of Hualien Tzu Chi Hospital between October 2019 to September 2020 were enrolled. The acute geriatric ward, an ACE unit, is the first and the only of its kind in eastern Taiwan and provides integrated care for older patients. The ACE unit provides age-friendly environments, patient-centered care, disability prevention and rehabilitation, medical care review, and early discharge planning. In addition to three geriatricians with expertise in the care of older adults, one trained geriatric resource nurse is involved in the team as a care manager. Extended team members include a clinical pharmacist, dietitian, social worker, as well as physical, occupational, and speech-language therapists. Multidisciplinary team meetings are conducted at least once weekly.We included patients aged ≥ 65 years who required acute inpatient medical care. Patients who were totally dependent for personal care before admission and those approaching the end of life were excluded. We also excluded those transferred to another unit within 24 h of admission, as they could not accept full ACE care and complete the assessments.All the following data were collected by the trained geriatric resource nurse. We collected frailty status as well as the baseline clinical and demographic characteristics within 48 h of admission.We obtained information on age, sex, principal diagnosis, length of stay, body mass index (BMI), Lawton Instrumental Activities of Daily Living (IADL) , Mini-MeThe FRAIL scale is a validated tool for frailty evaluation and is composed of the following five domains: fatigue, resistance, ambulation, illness, and loss of weight , 23. BasThe associations of FRAIL scale categories  with functional change at admission and before discharge were examined based on ADL, short physical performance battery (SPPB), and grip strength.Disability was assessed using the Barthel Index for ADL measurement , 25. BasThe SPPB is a simple measure of lower extremity performance using three-component tasks: static balance, gait speed, and chair stand . Static Grip strength was assessed using a hand dynamometer . The assessment was performed three times. All patients were instructed to hold the dynamometer with their dominant hand without squeezing their arms to their body in a standing or sitting position, depending on their ability , 28. TheWe divided the patients into three groups according to FRAIL score: robust (score = 0), prefrail (score = 1–2), and frail (score = 3–5). We used descriptive statistics to estimate the baseline clinical and demographic characteristics. One-way analysis of variance for continuous variables and chi-square test for categorical variables were used to compare population characteristics across three FRAIL groups. The difference in ADL, SPPB, and grip strength at admission and before discharge was determined using a paired sample t-test. We applied Pearson's correlation coefficient to evaluate the relationship between the length of stay and ADLs (including baseline ADL and ADL at admission). To assess whether frailty status was a predictor of functional recovery in an ACE unit, we employed multiple linear regression and examined the association between frailty status and the change in ADL (discharge ADL score minus admission ADL score) after adjusting for age, sex, CCI, BMI, MMSE, GDS-5, and PIM. We also applied multiple linear regression using frailty status, baseline ADL, length of stay, and principal diagnosis, as the independent variables for the ADL changes. A two-tailed probability value of < 0.05 was considered statistically significant. All statistical analyses were performed using the IBM SPSS Statistics for Windows, version 22 .n = 28, 24.6%), prefrail , and frail . The mean age was 79.8 ± 8.1 years, and 77 (67.5%) were females. The three most common causes of admission were urinary tract infection (38.6%), pneumonia (10.5%), and gastric ulcer (8.8%). The average length of stay was 6.4 ± 5.6 days. Most patients had multimorbidity . A comparison of the baseline clinical and demographic characteristics of the patients in the robust, prefrail, and frail groups are shown in Table Of the 120 patients who were admitted to the ACE unit, five who were totally dependent for personal care and approaching the end of life and one who was transferred to another ward on the same admission date were excluded. The remaining 114 participants were classified into three groups by FRAIL score: robust (P < 0.001). Regarding physical function, significant differences in SPPB  and grip strength  were found.Table P < 0.001; Fig. P = 0.008).The effect of the ACE unit on ADL and SPPB was significant in the different frail groups. All groups showed improved ADL and SPPB at discharge. The frail group had the most significant change in mean ADL score . However, the frail group showed no association with ADL change compared with the prefrail group . When frailty status, baseline ADL, length of stay, and principal diagnosis were used as independent variables, multiple linear regression still showed a significant association between frail group and changes in ADL  (Table Furthermore, multiple linear regression Table  showed tThis prospective observational study found that older patients in the ACE unit may experience varying degrees of functional improvement across different frailty classifications based on the FRAIL scale. Compared to robust patients, those classified as prefrail and frail were associated with more functional recovery between admission and discharge.Based on clinical evidence, ACE units could improve functional outcomes ; howeverThis study was the first to use the FRAIL scale at admission to evaluate whether different baseline frailty status is a predictor of recovery of ADL function in an ACE unit. We confirmed that patients classified as prefrail and frail were associated with more functional improvement. The International Conference of Frailty and Sarcopenia Research has suggested the FRAIL scale as a screening tool for frailty . It is aIdentifying the frailty status of patients in ACE units has below benefits that may contribute to the prevention or treatment of hospital-associated disability. During identifying the frailty status, the interdisciplinary team may be prompted with potential causes of frailty. For example, in patients with fatigue, in addition to treating acute illness, further investigation on possible related causes, such as postural hypotension, depression, hypothyroidism, vitamin B12 deficiency, and anemia, should be performed . MoreoveOur study showed that lower extremity physical function, as measured by SPPB, improved in the three frail groups. Physical function was described as the capacity of an individual to perform physical ADL . ADL evaThe strengths of this study included its prospective design, which helped in the tracing of nearly all acutely hospitalized older patients in the ACE unit. Moreover, the measurements of frailty and functional outcomes using the FRAIL scale, Barthel Index, SPPB, and grip strength were feasible in the acute hospital setting, which in turn facilitated the identification of the association between frailty and functional change. In addition, we used different functional outcomes, including ADL and physical function, thereby making the evaluation of the effect of the ACE unit on older patients with different degrees of frailty possible.This study has some limitations. First, our study excluded those patients with total dependence for personal care and approaching the end of life, which diminished the generalizability of our findings. However, patients with severe disabilities should be considered terminally ill and thus require care different from that in the frailty care spectrum; individual palliative care should be arranged . Second,In conclusion, the ACE unit was associated with functional improvement in older patients with frailty. Among the different frail groups based on the FRAIL scale, the prefrail and frail groups were associated with more functional recovery during hospitalization. These findings open the possibility for a shift from the traditional disease-focused care to a redesigned age-friendly care system that recognizes frailty status as an important clinical predictor of functional improvement.