We have previously identified a subset of diabetic sensorimotor polyneuropathy (DSP) patients with probable demyelination related to poor glycemic control. We aimed to determine whether the clinical characteristics and electrodiagnostic classification of nerve injury in diabetes patients with “demyelinating” DSP (D-DSP) differed from those diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) (CIDP + diabetes mellitus [DM]).D-DSP (56) and CIDP + DM (67) subjects underwent clinical examination and nerve conduction studies (NCS), and were compared using analysis of variance, contingency tables, and Kruskal–Wallis analyses.1c (HbA1c) of 8.2 ± 2.2%, 54% had CIDP + DM and 46% had D-DSP. CIDP + DM subjects were older (P = 0.0003), had shorter duration of diabetes (P = 0.005), and more severe neuropathy as indicated by Toronto Clinical Neuropathy Score (TCNS) (P = 0.003), deep tendon reflexes (P = 0.02), and vibration perception thresholds (VPT) . The mean HbA1c value for D-DSP subjects (8.9 ± 2.3%) was higher than in CIDP + DM subjects .Of the 123 subjects with a mean age of 60.5 ± 15.6 years and mean hemoglobin AThe clinical phenotype and electrophysiological profile of CIDP + DM patients is marked by more severe neuropathy and better glycemic control than in patients with D-DSP. These findings indicate that these two conditions – despite similarities in their electrophysiological pattern of demyelination – likely differ in etiology. Diabetic sensorimotor polyneuropathy (DSP) is a common complication of both type 1 and type 2 diabetes mellitus (DM) and is thought to occur due to hyperglycemia-related peripheral nerve damage. Classically, DSP results in axonal degeneration and progressive loss of nerve fibers, as indicated by reduced compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes, with normal or slightly reduced conduction velocities secondary to loss of the largest, fastest conducting axons  to those patients with diabetes diagnosed with CIDP (CIDP + DM). We aimed to determine if diabetes patients with D-DSP have unique profiles when compared to patients with CIDP + DM to allow the use of effective, targeted therapies.n = 27) and type 2 (n = 29) diabetes were seen between 2008 and 2012 as part of an ongoing longitudinal cohort study funded by the Juvenile Diabetes Research Foundation (Operating Grant No. 17-2008-715) and a cross-sectional cohort study funded by the Canadian Diabetes Association (Operating Grant No. OG-3-10-3123-BP). Diabetes subjects with CIDP were seen in clinic for management of their immune-mediated polyneuropathy between 1997 and 2012. All subjects were ≥18 years of age and had a confirmed diagnosis of type 1 or type 2 DM and either DSP or CIDP.One-hundred and twenty-three diabetes subjects with polyneuropathy were accrued for this study in the neuromuscular clinic of Toronto General Hospital (TGH) at University Health Network (UHN). DSP subjects with type 1 (1c), fasting plasma glucose, random elevated glucose with symptoms, or abnormal oral glucose tolerance test . Our current study involved the extraction of demographic data, clinical history, physical examination, laboratory results, and electrophysiologic data from the research database for DSP patients and previously coded charts for CIDP patients. None of the D-DSP subjects had a diagnosis of immune-mediated polyneuropathy or CIDP. The CIDP + DM group lacked specific tests or biomarkers to confirm the diagnosis of CIDP other than NCS and expert opinion. The Research Ethics Board of the University Health Network approved the current study protocol.As part of the initial cohort study, each participant underwent comprehensive medical and neurologic evaluation for the assessment of neuropathy-related symptoms and comorbidities, physical examination, and biochemical testing , vibration perception thresholds (VPT), and sural and peroneal NCS  or the Kruskal–Wallis test for nonparametric data. Correlation between peroneal compound motor action potential (CMAP) amplitude and conduction velocity was investigated using linear regression methods. P-values less than 0.05 were considered significant.Statistical analysis was performed using JMP . Demographic data were expressed as means ± standard deviation (SD) for normally distributed data, or median and interquartile range [IQR] for data not normally distributed. Differences in categorical variables were assessed using the 1c of 8.2 ± 2.2% (66 ± 24 mmol/mol). Of these subjects, 67 (54%) had CIDP + DM and 56 (46%) had D-DSP. CIDP + DM subjects were older (P = 0.0003) and had shorter duration of diabetes (P = 0.005) and higher diastolic blood pressures (P = 0.04) than D-DSP subjects. Subjects did not differ in terms of body mass index (BMI) (P = 0.51), systolic blood pressures (P = 0.91), and upper limb VPT , or in the presence of retinopathy (P = 0.24), nephropathy (P = 0.70), or hypertension (P = 0.11).The demographic data of the 123 type 1 and type 2 diabetes subjects categorized as having D-DSP or CIDP + DM are shown in Table P = 0.003), greater impairment of lower limb reflexes (P = 0.02) and more elevated lower limb VPT . A detailed comparison of lower limb reflexes is shown in Table The severity of neuropathy was increased in CIDP + DM subjects as indicated by the higher TCNS  and slower peroneal motor conduction velocities  than D-DSP subjects. However, the distal peroneal CMAP amplitude (P = 0.63) and F-wave latencies (P = 0.38), as well as sural SNAP amplitudes (P = 0.82), distal sensory latencies (P = 0.23), and sensory conduction velocities (P = 0.50) showed no difference. No difference in conduction block was observed between study groups. A positive linear correlation between peroneal distal CMAP amplitude and conduction velocity was found among D-DSP and CIDP + DM subgroups , with similar weak correlation strengths for D-DSP (r2 = 0.09) and CIDP + DM (r2 = 0.1) patients. Most importantly, the mean HbA1c value for D-DSP subjects (8.9 ± 2.3% [74 ± 25.1 mmol/mol]) was significantly higher than CIDP + DM subjects .CIDP + DM subjects had increased peroneal distal motor latencies  (Table P = 0.04) and a lower occurrence of hypertension (P = 0.02) than CIDP + DM patients.When the analyses were repeated for the CIDP + DM subjects compared to type 1 Table  and typeWe examined a cohort of type 1 and type 2 diabetes patients with D-DSP or CIDP + DM to compare their clinical characteristics and electrodiagnostic classification of nerve injury and observed that D-DSP patients have a unique clinical profile when compared to patients with CIDP + DM. Specifically, CIDP + DM patients are older, have better glycemic control, a shorter duration of diabetes, and more severe nerve injury than patients with D-DSP.1c values and lacked weakness on examination, so the demyelinating features on NCS in these patients are more likely to be caused by metabolic rather than inflammatory nerve damage. The higher HbA1c values in D-DSP patients suggests that suboptimal glycemic control plays a prominent role in the observed conduction slowing compared to CIDP + DM patients who likely have other factors leading to conduction slowing.In a previous study, different electrophysiologic behaviors were found to be linked to metabolic control in D-DSP such that demyelinating change on NCS indicates worse control and may afford the opportunity for intervention . Also, as clinicians might use NCS in the upper extremities to distinguish CIDP from D-DSP, exclusion of upper limb NCS may limit the observations.Misclassification is a potential error – there are no biomarkers to make a definitive diagnosis of CIDP and demyelination or conduction slowing on NCS is not a specific finding. However, the differences in clinical phenotype observed between the groups support the diagnostic classification. Also, the degree of demyelination used to define CIDP in this study are not as strict as in published criteria, but existing criteria are accepted as lacking high sensitivity and recent approaches employ more relaxed criteria (Koski et al. The treatment of the TCNS as a linear scale despite that it is a composite multiitem measure and the assumption that the response options per item have equal numerical value may not be valid (Stucki et al. The differentiation of CIDP from DSP in patients with diabetes is important due to the implications for therapy and prognosis. This study helps to define the clinical phenotype and electrophysiological profile of CIDP + DM patients and shows that they differ in DSP patients, even those with D-DSP. Future work directed toward finding a definitive biomarker for the diagnosis of immune-mediated polyneuropathies would have major therapeutic implications for all patients.


Hearing impairment is a prevalent and chronic condition in older people. This study investigated the relationship between cognitive function and hearing impairment in a Japanese population.A pure-tone average (0.5-2.0 kHz) was used to evaluate hearing impairment in 846 participants of the Iwaki Health Promotion Project who were aged at least 50 years old (310 men and 536 women). We also administered the Mini-Mental State Examination (MMSE), the Center for Epidemiologic Studies for Depression (CES-D) scale, Starkstein's apathy scale (AS) and the Short Form Health Survey Version 2 (SF-36v2). A multiple linear regression analysis assessed the association between hearing impairment and mental correlates.The overall prevalence of hearing impairment in this study population was 37.7%. The participants with hearing impairment were older and less educated compared to those with no hearing problems. We observed significant differences in the MMSE and AS scores between the mild/moderate to severe groups versus the non-impaired group. After adjusting for age, gender and amount of education, hearing impairment was significantly associated with MMSE and AS scores, but not with CES-D scores. Hearing impairment was significantly related to the social functioning (SF) and role emotional (RE) scores of the SF-36v2.Hearing impairment is common among older people and is associated with cognitive impairment, apathy and a poor health-related quality of life. Screening for and correcting hearing impairments might improve the quality of life and functional status of older patients. Age-related hearing impairment is a prevalent yet under-recognized health issue ,2. Previet al. [The association between hearing impairment and cognitive function has been recognized for many years . In a caet al.  reportedSome studies have also suggested that there is an association between hearing impairment and depression ,12, wherThe present study sought to clarify the relationship between hearing impairment and cognitive function in an older Japanese population. We also assessed the relationship between hearing impairment and apathy. To the best of our knowledge, this study is the largest to date to evaluate the association between hearing impairment and cognitive function in Japan.The study was conducted between June 2008 and June 2009. We recruited 846 volunteers who were at least 50 years old (310 men and 536 women) and had participated in the Iwaki Health Promotion Project. The Ethics Committee of the Hirosaki University School of Medicine approved the data collection for this study. All participants provided written informed consent prior to the study. We obtained demographic data  using self-questionnaires and interviews.A conventional audiometer  obtained air-conduction pure-tone thresholds in both ears at 500, 1, 000 and 2, 000 Hz. Using an average threshold over three frequencies for the better ear, we defined mild hearing impairment as participants who could not hear below 40 dB (to 25 dB) and moderate to severe hearing impairment as those who could not hear at higher thresholds than 40 dB.The Mini-Mental State Examination (MMSE) was used to measure the participants' global cognitive status by assessing their orientation to place and time, short-term memory and episodic long-term memory, as well as their ability in subtraction, sentence construction and oral language ability. The maximum score on the MMSE is 30 .et al. [To quantify apathy, we used the Japanese version of the Apathy Scale (AS) by Starkstein et al. -21. The The Center for Epidemiologic Studies for Depression (CES-D) scale was used to measure participants' depressive status ,23. ThisThe Short Form Health Survey Version 2 (SF-36v2) was used to assess participants' health-related quality of life (HRQOL). The SF-36v2 is a standardized international 36-item self-administered questionnaire that was translated, adapted, and validated for use in Japan . This meP < 0.05 to be significant. We analyzed the data using PASW Statistics (v. 18) for Windows.We computed descriptive statistics to describe the demographic and clinical variables. A one-way analysis of variance (ANOVA) was used to compare demographic and clinical characteristics between groups. The Dunnet test was used for post hoc comparisons. Pearson's correlation analysis was used to assess the relationship between SF-36v2 scores and hearing impairment. After adjusting for confounding demographic factors , a multiple linear regression analysis was used to examine the relationships between hearing loss and MMSE, CES-D, AS and SF-36v2 scores. We considered a value of The average hearing thresholds for participants who were 50-59, 60-69 and ≥70 years old were 19.9 ± 7.0 dB, 23.5 ± 8.0 dB and 29.4 ± 11.6 dB, respectively. We divided the participants into three groups according to their level of hearing impairment thresholds: none (< 25 dB), n = 527; mild (25-39 dB), n = 265; and moderate to severe (> 39 dB), n = 54. The prevalence of hearing impairment in our sample was 37.7%. Table Table Table Table This study evaluated the association between hearing impairment and cognitive function among a community-dwelling population in Japan. The prevalence rate of hearing impairment in this sample was 37.7%; furthermore, we observed an age-related increase of hearing thresholds among participants. We found a significant association between hearing impairment and cognitive function using the MMSE. Hearing impairment was also significantly related to AS scores, but not to CES-D scores.et al. [Previous studies have shown that hearing ability predicts cognitive function. Multiple cross-sectional studies ,27,28 haet al.  demonstret al. [Associations between hearing impairment and depression have also been reported. Some cross-sectional studies ,12,30,31et al.  did not et al.  did not et al. ,33 have et al. -36.In this study, hearing impairment was significantly associated with adjusted scores of SF-36v2 standardized scores in social functioning (SF) and role emotional (RE) domains. These results suggest that people with hearing impairment might experience more negative emotional reaction and social functioning limitations compared to participants without hearing problems. Conversely, previous studies ,9 have nThe mechanisms for the association between hearing impairment and cognitive function are not clear. One possible explanation for this relationship is that reductions in the quality or quantity of auditory input lead to structural or functional changes in the brain, which results in a decline of cognitive function. In this study, we found a relationship between hearing impairment and SF and RE scores on the SF-36v2. These aspects might cause cognitive decline or apathy. Another explanation might be that brain damage causes both hearing impairment and decline of mental function in older people. We did not image the brains of our participants, therefore we cannot evaluate this possibility.The current study has several limitations. First, this study was cross-sectional study, so we cannot determine whether hearing impairment causes cognitive decline and apathy. To do so, a follow-up survey will be necessary. Second, the MMSE was primarily administered verbally; however, one component requires participants to copy an overlapping pentagon. This section might be biased against participants with severe hearing and vision impairments. Third, because all participants were volunteers with interests in their health, they may be healthier than the general population. Thus, those not in the study may have poorer cognitive outcomes . This 'sHearing impairment is common among older people, and it is associated with cognitive impairment, apathy and poorer HRQOLs. Hearing impairment screening for older patients may not only improve patients' short-term QOL, but also identify those who are at increased risk for future cognitive decline and apathy. From a preventive standpoint, there is growing evidence that correcting hearing impairments can improve QOL and functional status in older people.The authors declare that they have no competing interests.NS conceived the study, designed the study, conducted the statistical analysis, interpreted the data and wrote the initial draft of the manuscript. SK had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. AS, HS and NYF contributed to study design and assisted in drafting the manuscript. TU and SN completed initial survey construction, recruitment of participants. SK and AN participated in the data collection and the interpretation of the results. All authors have approved the manuscript.


Hearing loss in children born before 32 weeks of gestation is more prevalent than in full term infants. Aminoglycoside antibiotics are routinely used to treat bacterial infections in babies on neonatal intensive care units. However, this type of medication can have harmful effects on the auditory system. In order to avoid this blood levels should be maintained in the therapeutic range. However in individuals with a mitochondrial genetic variant (m.1555A > G), permanent hearing loss can occur even when drug levels are within normal limits. The aim of the study is to investigate the burden that the m.1555A > G mutation represents to deafness in very preterm infants.This is a case control study of children born at less than 32 completed weeks of gestation with confirmed hearing loss. Children in the control group will be matched for sex, gestational age and neonatal intensive care unit on which they were treated, and will have normal hearing. Saliva samples will be taken from children in both groups; DNA will be extracted and tested for the mutation. Retrospective pharmacological data and clinical history will be abstracted from the medical notes. Risk associated with gentamicin, m.1555A > G and other co-morbid risk factors will be evaluated using conditional logistic regression.If there is an increased burden of hearing loss with m.1555A > G and aminoglycoside use, consideration will be given to genetic testing during pregnancy, postnatal testing prior to drug administration, or the use of an alternative first line antibiotic. Detailed perinatal data collection will also allow greater definition of the causal pathway of acquired hearing loss in very preterm children. Advances in neonatal intensive care have resulted in substantial improvements in outcome, in particular the survival of very preterm infants. HoweverInfection is a common occurrence during the neonatal period due to the underdeveloped immune system of the preterm infant, and can rapidly become life threatening. Aminoglycoside antibiotics are frequently used as a first line of treatment for suspected or proven bacterial sepsis. High efficacy, low levels of resistance and low cost make this group of medications an effective and recommended option. AminoglA genetic predisposition renders some individuals more susceptible to rapidly progressive, permanent hearing loss even when aminoglycoside levels are maintained within the therapeutic range. The most common predisposing mutation is the mitochondrial m.1555A > G variant, a maternally inherited genetic trait. Although the exact process of aminoglycoside induced deafness is unknown it is thought that the m.1555A > G mutation enables aminoglycosides to bind to the mitochondrial ribosomes more readily than the normal genetic sequence. This is thought to result in abnormal translation of mitochondrial proteins necessary for energy production. Hair cells in the inner ear are metabolically highly active and consequently have large numbers of mitochondria. In addition, aminoglycosides easily enter the hair cells but take a long time to be cleared.In susceptible individuals, a single dose of aminoglycoside may cause hearing loss. Early indications were that penetrance of deafness following aminoglycoside exposure was close to 100% in the presence of m.1555A > G. For example, in a study of European families with a history of maternally transmitted deafness and presence of the m.1555A > G mutation, all individuals who received aminoglycosides became deaf. FurtherThe Avon Longitudinal Study of Parents and Children cohort (ALSPAC) showed the prevalence of the mutation to be 1 in 520 children. AudioloThe primary aim of this study is to evaluate the contribution of the m.1555A > G mutation to acquired deafness in babies born at a gestational age of less than 32 weeks, who are likely to have received multiple doses of aminoglycoside antibiotics. Further to this, the study aims to calculate the relative odds of carrying the genetic variant and being in the deaf group versus the hearing group. Risk associated with gentamicin, m.1555A > G and other co-morbid risk factors will be evaluated using conditional logistic regression to determine potential gene-drug interactions in the context of other ototoxic risks.Case control study, with 5 controls for each index case.Any child born at 31 weeks and 6 days gestation or less with confirmed hearing loss (>40dBHL). Children with clear genetic syndromic causes for hearing loss will be excluded.This will include all children with hearing loss who were born at less than 31 weeks and 6 days gestation between January 2009 and December 2013. All children will have been treated in a Neonatal Intensive Care Unit (NICU) within the Greater London region. Participants will be identified through electronic databases, hearing assessment centres, neonatal follow up services and advertisements promoting the study.Each child recruited with hearing loss will be matched with five children with normal hearing. Control children will be identified through the Standardised Electronic Neonatal Database (SEND) which contains demographic and clinical information about infants admitted to neonatal units across London. Matching will be based upon gestational age (same number of completed weeks of gestation), sex  and neonatal unit on which they received their neonatal intensive care over the first two weeks after birth. Control children with partially complete or missing pharmacological records will be excluded on the premise that other matched control children will be identifiable with more comprehensive records.Index children will be invited to participate in the study via a letter sent by the audiological paediatrician responsible for their care. This will enclose information about the study and parents who require further information or would like to participate will be asked to return a short form to indicate their willingness to speak to the research team. The research nurse will telephone the parent(s), explain the study further and arrange a convenient time to meet parents if they wish to participate. Parents who identify themselves to the research team via newsletters or advertisements will be spoken to directly by the research team. Written informed consent will be obtained for genetic testing of a saliva sample, and to extract data from neonatal and audiological clinical notes. During a subsequent home visit saliva samples will be taken if testing for m.1555A > G has not been undertaken as part of clinical care. Saliva samples will be collected using an Oragene collection kit and transported to the laboratory for testing. DNA is extracted using standard procedures and analysed by polymerase chain reaction and restriction enzyme digestion, followed by sequence confirmation by bi-directional Sanger sequencing in mutation-positive cases.Matched controls will be identified though the national neonatal research dataset. Parents of control children identified will be invited to participate by letter sent by the clinician responsible for their neonatal care. Those wishing to participate in the study will contact the research team as above.Children identified to have the mutation will be recalled and the presence of m.1555A > G reconfirmed by analysis of DNA extracted from a second sample. Families confirmed to have the mutation will be offered genetic counselling. Since mitochondrial DNA is maternally inherited, there are additional implications for extended maternal family members, who will also be offered genetic counselling.Clinical data will be extracted from the neonatal and audiological medical notes for all children using an agreed proforma to record details of demographics, clinical events and therapeutic history, with serum levels of drugs as available. Data will be collected by day after birth to identify coincidence of risk factors. Pharmacy records will be examined to confirm aminoglycoside exposure, including dose, duration, number of courses and blood level concentrations. Audiological records will be reviewed to define the severity and pattern of hearing loss.Data will be encoded for data analysis using double entry into an automated error detection system in SPSS (IBM Inc) in its latest version. Subsequently data will be checked for outliers, prior to analysis using Stata (Version 13).The annual birth-rate in London is approximately 120 000, (600 000 in 5 years). It is estimated that 1% of these babies have a birth weight of less than 1501 g. This giThus the total study population should include between 180–720 children, 30–120 index and 150–600 controls.The burden of disease will be calculated as the proportion (and 95% CI) of children with hearing loss that have the mutation, using the method of Wilson. The odds ratio of children with the m.1555A > G mutation having hearing loss will be calculated using Fisher’s exact test. The analysis for the burden of disease and the relative risk of deafness for those with the mutation will initially include all cases. This will be repeated excluding children who received less than one dose of aminoglycoside medication, and repeated again excluding those who received fewer than two doses.The antecedents and associates of hearing loss will be determined using conditional logistic regression to account for matching. Factors will be evaluated individually and as combinations occurring simultaneously to account for additive risk.The study has been approved by the National Research Ethics Service  and is registered under the National Institute for Health Research (NIHR) Portfolio scheme. The study is funded by a financial grant from Action on Hearing Loss; the funding source has had no input into the design or execution of the research study.We aim to investigate the contribution of m.1555A > G to deafness in preterm infants where aminoglycosides are likely to have been used and to evaluate this role within the occurrence of multiple risk factors for hearing loss identified during neonatal intensive care. We hypothesise that the mutation will make a significant contribution to deafness even when aminoglycoside levels are maintained within the therapeutic range. From our clinical experience, we suspect that in some cases, single courses of aminoglycosides may be tolerated but multiple courses may not be, possibly due to the accumulation of the medication in the hair cells of the inner ear, which can take several months to clear. Multiple courses of aminoglycosides during the neonatal period would thus inhibit the clearance process.Alongside such a potential interaction, to date multiple studies have failed to provide consistent evidence for specific risk factors. Intriguingly one small study has reported that it is the coincidence of risk factors that may determine the development of hearing loss. A rangeShould m.1555A > G be implicated in the aetiology of neonatal hearing loss in very preterm babies, then alternative strategies may be necessary to manage preterm neonatal sepsis in affected babies.Alternative first line antibiotics could be used instead of aminoglycosides. Using more broad spectrum agents runs the risk of increasing patterns of bacterial resistance in the relatively closed microbiological setting of neonatal intensive care. Further, owing to low cost and the synergistic effects of aminoglycosides, their use is preferred by many services for babies at risk of life threatening infection, considering that the risk of aminoglycoside associated hearing loss is as yet unsubstantiated in newborn babies.A further alternative would be universal genetic screening (of pregnant women) or focussed genetic screening of babies prior to treatment, which is at present impracticable. Due to Mitogent is designed to provide critical answers concerning the aetiology of acquired hearing impairment in very preterm babies and specifically to identify the role of aminoglycoside toxicity in individuals with m.1555A > G.ALSPAC: Avon longitudinal study of parents and children cohort; dBHL: Decibels hearing level; NICU: Neonatal intensive care unit; SEND: Standardised electronic neonatal database; CI: Confidence interval; NIHR: National institute for health research.The authors declare that they have no competing interests.KC wrote the first draft and produced the final version. NM, SR and MB-G conceived the idea and obtained funding. Each has reviewed this paper and approved the final version.KC is the research fellow conducting the study; NM is a professor of neonatal medicine and has a major interest in perinatal influences on long term outcomes; SR is a Reader and Consultant in metabolic and mitochondrial medicine; MB-G is a professor of clinical and molecular genetics specialising in genetic hearing loss.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/14/66/prepub


Neonatal hyperbilirubinemia is one of the most important factors affecting the auditory system and can cause sensorineural hearing loss. This study investigated the relationship between behavioral hearing thresholds in children with a history of jaundice and the maximum level of bilirubin concentration in the blood.This study was performed on 18 children with a mean age of 5.6 years and with a history of neonatal hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and brainstem evoked responses were evaluated in all children.Six children (33.3%) had normal hearing thresholds and the remaining (66.7%) had some degree of hearing loss. There was no significant relationship  between the mean total bilirubin levels and behavioral hearing thresholds in all samples. A transient evoked emission was seen only in children with normal hearing thresholds however in eight cases brainstem evoked responses had not detected.Increased blood levels of bilirubin at the neonatal period were potentially one of the causes of hearing loss. There was a lack of a direct relationship between neonatal bilirubin levels and the average hearing thresholds which emphasizes on the necessity of monitoring the various amounts of bilirubin levels. High bilirubin level at birth has been considered as one of the most important factors affecting the auditory system. Although this disease does not have thoughtful consequences in most infants, in the absence of appropriate treatment, high levels of blood serum bilirubin can result in acute encephalopathy and brain damage ,2. When Studies that reviewed audiological findings in children with a history of neonatal hyperbilirubinemia have primarily used electrophysiological and non-behavioral tests such as auditory brainstem response (ABR). For instance, the study of Jiang et al on infants with a history of neonatal hyperbili- rubinemia revealed that the threshold of ABR response recorded in these infants was significantly increased . In the Evidence suggests that lower levels of bilirubin may cause minor encephalopathy that known as bilirubin- induced neurological dysfunction (BIND). In this case, the hearing impairment has been reported alone and without any other signs of kernicterus . The relConsidering the results of these studies and assuming that different degrees of neonatal hyperbilirubinemia can cause different degrees of hearing impairment, our study investigated the behavioral hearing thresholds in children with a history of neonatal jaundice and reported the frequency of hearing impairment. This study also addressed the relationship between the average hearing thresholds and level of serum bilirubin.This study was performed from January to June 2012 at the audiology department of faculty of rehabilitation in Tehran University of Medical Sciences. Our study was performed on 18 children aged 2.4 to 11 years (mean 5.6±2.5 years) and with a history of neonatal hyperbilirubinemia. Of these, 10 were girls (55.6%) and 8 (44.4%) were boys. Additional information regarding the children is summarized in At the initiation, a case history was obtained for each child. Subsequently, following ensuring of normal middle ear function using a calibrated Interacoustics AZ26 tympanometer, behavioral air conduction hearing thresholds at frequencies of 500, 1000, 2000 and 4000 Hz were recorded using a calibrated Interacoustics AC40 audiometer. Threshold acquisition procedure was different according to the age of the child. In children aged less than 5 years, the conditioned play audiometry (CPA) was used and in children of 5 to 11 years, conventional adult’s audiometry was performed. Visual reinforcement audiometry (VRA) was used only in a 2.4 year old child, to gauge the hearing thresholds.According to numerous studies, in cases with neonatal hyperbilirubinemia, hearing impairment was attributed to cochlear and retrocochlear structures -15. To iSPSS version 18 was operated in 0.05 significant levels. Moreover, Colmogrov-Smirnov test was used to define normal distribution of data. To investigate the relationship between serum bilirubin levels and mean hearing thresholds, spearman correlation was used.None of the children had a history of birth hypoxia. Two cases (11.1%) had a history of premature birth (prior to 37 weeks) and both had abnormal behavioral hearing thresholds. None of the children had a history of very low birth weight (less than 1500 g). Overall, 6 subjects (33.3%) had normal behavioral hearing thresholds and 12 subjects (66.7%) had some degree of hearing loss. One of the children had moderate hearing loss, four patients with moderate to severe hearing thresholds and seven had severe to profound hearing loss.Average behavioral hearing thresholds in four frequencies measured, standard deviations, upper bound and lower bound of thresholds, in cases with hearing impairment, had been presented in TOAE responses were recorded bilaterally and only in children with normal hearing. Generally, in 12 ears (33.3%), there was an acceptable response. Amplitude of responses was in the range of 5.3 - 22.2 dBSPL, with a mean of 12.8 ±4.9 dB. All normal hearing children had normal ABR responses. Changes in the ABR response in hearing impaired children ranged from no detectable wave I to total absence of response. Of 12 hearing impaired subjects, ABR response was seen bilaterally in 4 patients. None of hearing impaired cases had the wave I and only waves III and V were recorded subsequently. Due to the small number of hearing impaired cases with recordable ABR response, statistical evaluation to assess the significance of absolute and interpeak latency findings was not possible. In hearing impaired children, the wave form was partly distorted. Wave III was seen only in one patient. History of hearing tests had been performed in these children revealed that OAE and ABR responses in most of them had been unchanged over the time. Only three of them had TEOAE response at birth which was removed following a few months. ABR response was not identifiable in these children at birth however, at the time of this study, ABR had been recorded.Assessing the relationship between bilirubin levels and average hearing thresholds at four frequencies of 500, 1000, 2000 and 4000 Hz in both ears showed that there was no significant correlation between serum bilirubin levels and the mean behavioral hearing thresholds of the total sample of 18 children, 36 ears . Furthermore, a significant correlation was not observed between behavioral hearing thresholds in cases of SNHL  with serum bilirubin levels .Average hearing thresholds of children in this study had a range of normal hearing to profound hearing loss. Overall, two of the children had a history of preterm birth and in both the cases there were some degree of hearing loss. Bilirubin toxicity affects the performance of the auditory nerve in several ways. In general, the more central nervous system is exposed to the bilirubin, the more impact on hearing performance will occur . Since iThe present study showed that there is not any considerable relationship between the peak serum bilirubin levels during infancy and behavioral hearing thresholds. In other words, it is not possible to establish a direct connection between peak serum bilirubin levels and hearing thresholds. These findings are consistent with the results of previous studies on infants with a history of neonatal hyperbilirubinemia. In previous studies on neonatal jaundice, it has been reported that there is no considerable relationship between abnormalities of ABR amplitude and latency values and maximum levels of bilirubin in neonatal period ,19. HoweAccording to Rhee and colleagues (1999), in cases of neonatal hyperbili- rubinemia, the location of hearing impairment is outside of the cochlea and cochlear function will be unaffected . In contAuditory neuropathy spectrum disorder (ANSD) is defined as the presence of OAEs and/or cochlear microphonics (CMs) associated with severe ABR abnormalities or absent of ABR response ,23. As mThe findings of this study increase knowledge of the effects of neonatal hyperbilirubinemia on hearing. Inability to provide appropriate services to reduce dangerous levels of bilirubin can lead to chronic and permanent hearing impairment which has been reported in almost 10 percent of children with a history of neonatal hyperbilirubinemia . Using tThe present study showed that increased blood bilirubin levels in the neonatal period can be considered as one of the causes of hearing loss. Based on our findings, neonatal hyperbilirubinemia can cause abnormalities in auditory evaluations, including behavioral audiometry, without developing kernicterus. However, it seems that there is not any clear and direct relationship between serum bilirubin levels and hearing thresholds. Therefore, behavioral hearing thresholds and hearing system impairment cannot be estimated solely based on maximum bilirubin levels at birth.


Rhynchohyalus natalensis, that possesses an extensive lateral diverticulum to each tubular eye. Each diverticulum contains a mirror that focuses light from the ventro-lateral visual field. This species can thereby visualize both downwelling sunlight and bioluminescence over a wide field of view. Modelling shows that the mirror is very likely to be capable of producing a bright, well focused image. After Dolichopteryx longipes, this is only the second description of an eye in a vertebrate having both reflective and refractive optics. Although superficially similar, the optics of the diverticular eyes of these two species of fish differ in some important respects. Firstly, the reflective crystals in the D. longipes mirror are derived from a tapetum within the retinal pigment epithelium, whereas in R. natalensis they develop from the choroidal argentea. Secondly, in D. longipes the angle of the reflective crystals varies depending on their position within the mirror, forming a Fresnel-type reflector, but in R. natalensis the crystals are orientated almost parallel to the mirror's surface and image formation is dependent on the gross morphology of the diverticular mirror. Two remarkably different developmental solutions have thus evolved in these two closely related species of opisthoproctid teleosts to extend the restricted visual field of a tubular eye and provide a well-focused image with reflective optics.We describe the bi-directed eyes of a mesopelagic teleost fish,  A more rudimentary accessory retina, which receives only unfocused lateral illumination, coats the medial wall of each tube eye –6. AlthoHigh sensitivity, which is the primary prerequisite for the eye of an animal that resides in the low light levels offered by the deep sea, requires a large pupil. Most mesopelagic fish, however, are relatively small, making the possession of a large eye, normally required for an enlarged pupil, problematic. Tubular eyes can therefore be regarded as the central portion of a normal spherical eye that has been laterally reduced ,7, allowDorsally directed tubular eyes will maximize sensitivity to downwelling daylight against which animals higher in the water column will cast a silhouette. However, at many times of day, and in deeper water, the dominant source of illumination in the deep sea is not sunlight but bioluminescence –14, whicMacropinna microstoma) overcomes the limited visual field of a dorsally directed tubular eye by using extensive eye movements [At least one species  was caught in the Southern Tasman Sea Abyssal Basin (41°6.2′ S/152°21.8′ E) between 800 and 1000 m depth. It was photographed (A single (a)−1) to which was added the magnetic resonance imaging (MRI) contrast agent, 1% ionic Gd-DTPA , prior to MRI following a protocol developed for zebrafish [2*-weighted three-dimensional FLASH sequence with the following acquisition parameters  image processing software.The fish was removed from the storage medium and rehydrated by immersion for 2 h in a series of reducing concentrations of ethanol . After rehydration, the fish was placed overnight in 0.1 M phosphate buffer saline : recept(b)After MRI examination, the isolated eyes were postfixed in 2.5% glutaraldehyde and 1% osmium tetroxide. After removal of the lenses, the eyes were embedded in Epon, serially sectioned at 25 µm and mounted on plastic slides. Sections were photographed on a Zeiss stereomicroscope and selected sections and areas were re-sectioned at 1 µm or 80 nm. Some of the thick and semi-thin sections were stained with a mixture of methylene blue and Azur II. In order to test the refractive properties of structures, unstained sections were examined in a combination of dark-field and polarized light illumination (see  for deta(c)mageJ v. 1.46 64 bit for Mac OSX [atlab v. R2012b  model of the diverticulum in which the fate of rays entering the eye's ventral cornea was traced in two dimensions (i.e. in the plane of the section). The model's premises included: the diverticulum's function is to focus light from distant point sources onto the OLM; all of the OLM and mirror surface is used in image formation; the axial orientations of the rod outer segments (ROSs) converge at a point outside and lateral to the eye; the eye has a primary axis, rays entering at this angle being focused at the centre of the OLM; and ROSs have an acceptance angle beyond which incident rays are fully rejected. The acceptance angle was calculated to be ±19.95° using ROS and extracellular fluid refractive indices of 1.4106 and 1.335, respectively, from the data of Sidman [A photomicrograph of a midline dorsoventral section of the ocular diverticulum was digitized using I Mac OSX  to delinf Sidman , as usedf Sidman , and thef Sidman . The mirf Sidman , some oc(d)et al. [The thickness values used for the crystal layers and cytoplasm gaps are summarized in the results and correspond to a disordered ‘chaotic’ stack structure. Using this histological information from the mirror of the ocular diverticulum, it is possible to estimate the spectral, angular and polarization properties of the reflectivity of this class of crystal stack by using the optical transfer matrix methods  for phyet al. ,30, whicet al. ,30,31. Iet al. ,31. Impl3.(a)R. natalensis, like that of other opisthoproctids, consists of both a tubular portion and a lateral diverticulum. The dorsally directed tube eyes are most apparent in dorsal view (b), while the cornea of the diverticulum can be seen when viewed from the side or from below . The scleral walls of the eye are lined internally by a choroidal argentea and therefore appear silvery (d). The eye, like that of some other opisthoproctids, lies within a wide, dome-like dermal transparent capsule.The eye of sal view b, while om below c,d. The  silvery d. The eyRhynchohyalus is similar to that in mobile eyes of M. microstoma [Rhynchohalyus too may be capable of extensive eye movements .The organization of the extraocular muscles in crostoma  suggestid), MRI scans  and histological section (figure 1f). It runs down the entire length of the tubular eye exceeding its ventral margin by several millimetres . The lateral wall of the diverticulum is relatively flat and lined by an argentea, except for an oval transparent area  facing approximately 45° ventro-laterally. Seen from the ventral side, this cornea has a conspicuous notch medially that would admit light not only from directly ventral but possibly even from the contralateral side (figure 1c). Apart from the epithelial outer lining, the transparent cornea is composed of dense fibro-collagenous tissue and/or irregular plates of hyaline cartilage (b).The diverticulum, rostro-lateral to the tube eye, is readily apparent in photographs d, MRI scartilage b.Figure(b)R. natalensis tube eye is approximately 250 µm thick and includes four layers of rods each between 25 and 30 µm long and about 3 µm in diameter ; it has no obvious specialization such as an area of increased photoreceptor density (f). The thin retinal pigment epithelium contains numerous melanosomes and sparsely distributed tapetal crystals. This main retina extends about 2 mm up the medial walls of the tubular eye, where there is a sharp transition to the accessory retina which shows the normal layers of a retina but at a substantially reduced total thickness (100–150 µm) and includes one or two rows of short (15 µm) ROSs (g). Interestingly, towards the dorsal margin of the accessory retina there is a region, about 5 mm wide, where rod thickness and density is increased, with one or two additional rod layers (d). On the lateral side of the tubular eye, and especially lining the septum separating the diverticulum from the main eye, the accessory retina is reduced to a simple ciliary epithelium lacking photoreceptors or other retinal cells. In the diverticulum, the retina, which is little different to that of the main retina in the tube eye, is restricted to the flat lateral wall (a).The main retina of the  density f. The thµm) ROSs g. Intered layers d. On theral wall a.(c)R. natalensis cannot be illuminated directly  and photoreceptors in the diverticular retina can essentially only be illuminated by light reflected from the medial wall of the diverticulum. In D. longipes, with a similarly positioned diverticular retina, indirect illumination and a focused image is achieved via a highly reflective medially positioned mirror [R. natalensis, which also has a mirror inside the diverticulum eye that was observed in the fresh specimen and can be seen through the cornea (d).The lateral diverticular retina of d mirror . It seeme cornea d.c). Lining the diverticular face of the septum are elongated cells containing three to four layers of thin and empty ‘ghost-like’ spaces. Owing to their similarity to the reflective argentea on the lateral wall of the diverticulum (a), we are confident that the empty spaces correspond to reflective crystals, probably guanine (by reference to other silvery reflective tissues in teleosts), that have dissolved during the long interval between fixation and preparation for histology. A similar effect can be seen by the silvery appearance of the freshly caught specimen disappearing in the preserved specimen. Using dark-field illumination and polarized light, one or two thin lines of residual reflecting particles are observed . The crystal ghosts are separated by leaflets of cytoplasm, both of which were measured (see below). Their orientation is always parallel to the basal membrane of the septum . The space between the presumed guanine crystals and the basal lamina, separating the epithelial structures from the vitreal cavity of the diverticulum, appears artificially swollen with loosely arranged fibrous material and scattered melanosomes.The central component of the septum dividing the tubular portion of the eye from the diverticulum is a choroidally derived layer (see below) containing capillaries of varying diameter, numerous melanocytes and loose fibro-collagenous tissue, lined on both sides by a prominent basal membrane of which the one facing the ciliary epithelium of the tubular eye corresponds to Bruch's membrane c. Liningrticulum a, we are(d)a). At the ventral margin of the diverticular retina next to the cornea, the diverticular retina ends abruptly (e) and includes a short region resembling the proliferation zone that forms the retinal margin in ‘normal’ hemispheric eyes. At the ventral retinal margin, the retinal pigment epithelium and retina are reduced to a thin bilayered sheet, corresponding to a ciliary epithlium, that wraps around this region and continues dorsally over the surface of the retina. It is accompanied by a thin second layer of fibrocytes and connective tissue corresponding to the choroid. These layers cover the retina proper on its vitreal surface and run dorsally .To understand the origin of the reflective crystals in the medial wall of the diverticulum, it is necessary to examine the lateral wall of the diverticulum, which consists of the following well-developed layers : the retina, a choroid consisting of an inner vascular layer, a layer of melanocytes and a well-developed argentea, covered externally by a cartilagenous sclera a. At theabruptly e and incFurther dorsally, the diverticular retina thins and continues as ciliary epithelium . The inner epithelia derived from the retina and choroid, however, reflex ventrally and form the inner surface of the diverticular septum. On reaching the septum, the inner choroidal layer once more expresses the argentea, thereby forming the diverticular mirror. Medial to this, choroidally derived melaoncytes and vasculature, together with the ciliary epithelium, form part of the septum separating the diverticulum from the tube eye.(e)The ray-tracing model was relatively insensitive to the exact mirror surface  considered, but a significant improvement in eye performance was obtained when the angles of the plates of the mirror were allowed to diverge slightly from being exactly parallel to the mirror's surface. A series of tracings, for rays entering from different distant points in the latero-ventral visual field, and in which plate angles in the mirror diverge from surface tangents by ±5° about a mean of +5°, is shown in (f)n = 25) in thickness, the average thickness of the putative guanine crystals being 0.41 μm , with an average length of 3.27 μm . The thickness of the crystals is considerably greater than is required for an ideal narrowband quarter-wave multilayer ‘stack’ that is tuned to optical wavelengths. This would require a crystal thickness of approximately 0.04–0.09 μm [Trichiurus lepturus and the silver scabbardfish Lepidopus caudatus [Cyprinus carpio [Histological examination of the diverticular mirror showed that, typically, it comprised three to four leaflets of crystals separated by layers of cytoplasm each about 0.11 μm . As rodructures ,31,33, b4.R. natalensis.Although some invertebrates use mirrors to form images –36, to oR. natalensis eye [There has been a previous description of the nsis eye  that difnsis eye ,3,5. It D. longipes [R. natalensis appear similar, they differ in important respects. In D. longipes, the angle of the reflective plates varies considerably with position in the mirror, forming a Fresnel-type reflector in which reflective plates are far from being parallel to the mirror's surface. In R. natalensis, however, the gross geometry of the diverticular eye dictates that the reflective plates should lie almost parallel to the mirror's surface for a well-focused image to be obtained, although some small divergence from the surface tangent, unresolvable in our specimen, is predicted by our two-dimensional ray-tracing models. Naturally, three-dimensional ray tracing would provide a more definitive understanding of the focusing potential of the diverticular mirror but this will require access to tissue in better condition, both in terms of gross morphology and in terms of reflective plate histology. In the interim, two-dimensional ray tracing of a midline section of the diverticular eye (a region where we have most confidence of the structure's anatomy) demonstrates that rays in a vertical plane originating from a point source in the latero-ventral visual field can be brought to a good focus. This conclusion, a priori, is not a forgone conclusion and shows that the medial wall of the diverticulum is potentially capable of image formation by reflection, based largely on its shape and distance from the retina, with image quality being further enhanced by very small angular departures of the reflective plate angle from being parallel to the mirror's surface. In addition, despite having relatively few crystal layers, the predicted spectral and angular insensitivity of the reflectivity of the disordered crystal stack is suggestive that the structure preserves spatial information when focusing rays upon the ROSs. Most strikingly, in D. longipes, the mirror originates from the retinal pigment epithelium, whereas in R. natalensis it derives from the choroidal argentea. This major ontogenetic difference suggests differing evolutionary origins of the diverticular reflectors in the two species, despite their close phylogenetic affinity and the ultimately convergent function and adaptive value of the diverticular mirrors.Although the reflective diverticula of longipes  and R. nR. natalensis and previously for D. longipes [Winteria sp. and Opisthoproctus sp. [R. natalensis and elsewhere for D. longipes [B. exilis [The apparent complexity and seeming perfection of the conventional vertebrate eye has sometimes been taken as evidence against the very idea of evolution although, in truth, the eye is far from perfect and no more complex than most other organs. In fact, as Darwin himself realized , the exilongipes , remain ctus sp. ,3,5 to tlongipes  or to th. exilis . This fa


Objectives. To reviewour experience of conducting auditory brainstemresponse (ABR) test on children in the operating roomand discuss the benefits versus limitations of thispractice. Methods. Retrospectivereview study conducted in a pediatric tertiary carefacility. A total of 267 patients identified withusable data, including ABR results, medical andsurgical notes, and follow-up evaluation.Results. Hearing status successfullydetermined in all patients based on the ABR resultsform the operating room. The degrees and the types ofhearing loss also documented in most of the cases. Inaddition, multiple factors that may affect theoutcomes of ABR in the operating room identified.Conclusions. Hearing loss in childrenwith complicated medical issues can be accuratelyevaluated via ABR testing in the operating room.Efforts should be made to eliminate adverse factors toABR recording, and caution should be taken wheninterpreting ABR results from the operating room. About 2 to 3 of every 1000 children are identified with hearing loss at birth each year in the United States, and hearing impairment is, in fact, the most common sensory deficit in the pediatric population . Late-onWhile studies have shown that ABR test is a reliable and an objective method to assess children's hearing sensitivity –10, the A retrospective study, approved by the Institutional Review Board at Children's Hospital Boston, was conducted on children who had ABR test completed in the operating room in a pediatric tertiary care facility from 2007 to 2010. Our database included 452 ABR tests completed in the operating room during the study period. A total of 267 pediatric cases, most of them young children, were selected for a thorough review and analysis. All selected cases had sufficient information in their medical records, which include ABR results from the operating room, medical and surgical procedure notes, and follow-up evaluation documents. All audiological evaluations were carried out by licensed audiologists. ABR testing in the operating room was performed after ear examination under the microscope by a pediatric otolaryngologist while patients were under general anesthesia. Cerumen was removed when present before ABR testing. Other otologic procedures, when deemed necessary, were also performed by attending physicians/surgeons before ABR testing. These procedures included myringotomy, suction of middle ear effusion, and tube placement when necessary. The ABR was recorded with Bio-logic Navigator Pro Evoked Potential system  using Children's Hospital Boston pediatric protocol. Specifically, stimuli (clicks and tonebursts), calibrated in dB normal hearing level, were presented at 38.1 per second via insert phones. Electroencephalographic signals were collected via surface electrodes and averaged. Thresholds of ABR were determined by the lowest intensity level at which the wave V was present. If the wave V of ABR was not identified with the highest intensity stimulus, extra recordings with both rarefaction and condensation clicks were made to investigate the presence/absence of the cochlear microphonics. Follow-up audiological evaluation was conducted during return visit when patients recovered from the surgical procedures, usually within 3 months. Age-appropriate behavioral test procedures, for example, VRA, CPA, or conventional pure-tone audiometry, were typically performed. In some cases, a repeat of ABR testing was conducted due to inability to complete behavioral tests or lack of cooperation from the patients. For each patient, frequency-specific hearing thresholds were documented and stored for future analysis. U test) was carried out using the Statistical Package for Social Science  software. Both descriptive and qualitative analysis was performed in this study. For all patients, clinical diagnosis, the types of hearing loss, and the degree of hearing loss, so forth were summarized. We were able to collect hearing results from ABR completed in the operating room and postoperative examination from 121 children with OME, and comparison analysis was conducted for this subgroup of patients. The mean of thresholds at three frequencies, 1000, 2000, and 4000 Hz, was calculated and defined as the averaged hearing threshold. Analysis of variance (ANOVA) and nonparametric testing  had normal hearing. Among the other 209 children with hearing loss, 94 patients 35.2%) were found with mild loss, 75 patients (28.1%) with moderate loss, 21 patients (7.9%) with severe loss, and 19 patients (7.1%) with profound loss. In addition, we were able to identify the types of hearing loss in most of our patients. Over 60% of the children identified with hearing loss had conductive loss while about 15% of them had sensorineural loss. In addition, mixed hearing loss was seen in 17 patients (8.1%). There were 8 patients whose hearing loss was consistent with auditory neuropathy spectrum disorders. Based on the available results, the type of hearing loss could not be determined for the remaining 26 patients. The above findings are summarized in Tables 5.2% wereBy reviewing patients' medical records, we identified a number of medical conditions or events that are known to be associated with hearing loss, as summarized in During our recordings of ABR in the operating room, we observed several factors that could affect the outcomes. First, the background noise level in the operating room, in some cases, was extraordinarily high due to the use of multiple medical devices, which could create elevated ABR thresholds at lower frequencies such as 500 and 1000 Hz. Second, electromagnetic interferences from power sources, medical equipment in the operating room, and patients' own medical devices  could degrade ABR responses, which made the ABR waveforms unclear and difficult to read, resulting in overestimation of hearing loss. Third, the presence of middle ear fluid could influence the hearing results from the ABR testing even if the fluid was removed surgically, more significant in the cases with mucoid than in the cases with serous effusion. Finally, the ABR could be affected by patients' physiological and neurological status which might be altered by anesthesia medications. These factors are summarized in P < 0.01). Since the majority of our patients had OME, we decided to do further analysis on this group to see if there were any other factors of significance. Among the 153 children with suspected OME, we were able to collect pre- and postoperative hearing results in 121 patients. We divided them into three groups based on the procedures they received in the operating room. Group 1 included 47 patients (69 ears) who underwent microscopic examination with no middle ear effusion found; Group 2 included 13 patients (18 ears) who underwent myringotomy only with no tube placement; Group 3 included 61 patients (83 ears) who underwent myringotomy and tube placement. For patients in Group 1, the averaged hearing threshold from ABR was 3.5 dB (±3.5) higher than the follow-up audiological evaluation. In Group 2, the averaged hearing threshold from ABR was 4.0 dB (±3.5) higher than the follow-up audiological evaluation. In Group 3, the averaged hearing threshold of ABR from the operating room was 9.4 dB (±10.6) higher than the follow-up audiological evaluation. Comparison analysis showed that the averaged hearing threshold discrepancy between ABR from the operating room and the follow-up audiological evaluation was significantly different among the three groups (Although the averaged hearing threshold discrepancies between the ABR from the operating room and the follow-up audiological evaluation seemed to be relatively small in all groups, the results varied greatly among patients. Across the three groups, there were 16 ears that had average hearing threshold difference of greater than 20 dB, with the majority of these ears being patients in Group 3. In all groups, threshold discrepancy between the ABR from the operating room and the follow-up audiological evaluation was notably higher at 1000 Hz than that at 2000 and 4000 Hz. One common goal in identification of hearing loss in children among hearing care professionals, including otolaryngologists and audiologists, is making an accurate diagnosis as early as possible so that children with hearing loss can receive appropriate treatment and habilitation to avoid delays in speech and language development. Clinically, audiologists will choose age-appropriate behavioral evaluation methods to obtain hearing thresholds. ABR test may be used in certain cases for difficult-to-test children to estimate their hearing sensitivity although its value remains debatable among professionals when it is used in the operating room. Our experience of performing ABR testing in the operating room, as shown in our study, is mostly successful, and our findings are tremendously valuable in clinical care of pediatric patients with hearing concerns. Not only are we able to define the hearing status for the most difficult-to-test children with a variety of serious medical issues, but we are also able to determine the degree and the type of hearing loss for the majority of the patients. By doing so, we have provided appropriate recommendations for their much needed treatment and habilitation. At the same time, we also gained more knowledge of medical conditions and events that are linked to hearing loss. While we are confident in the justification of using ABR in the operating room , 15, we Performing ABR testing in the operating room can be, at times, a challenge. Through the process of conducting hundreds of ABR tests in the operating room, our audiology staff has experienced their success and difficulties in this task and our best practice have evolved. Efficiency of troubleshooting adverse ABR recording conditions, for example, eliminating electromagnetic inferences and minimizing factors or events that may degrade ABR waveform, has improved among our audiologists. ABR testing in the operating room, unlike the behavioral hearing tests, is not a direct measure of patients' hearing sensitivity. Accordingly, audiologists have to adjust their routine in explaining the audiologic results, improve their counseling skills, and provide more appropriate recommendations regarding patients' hearing loss to their parents. At last, better coordination and communication with other medical professionals in the operating room, such as the nurses, the surgeons, and anesthesiologists, is a key for audiologists to achieve the goal of accurate hearing assessment for children with complicated medial issues. Based on our study, we have concluded that ABR testing can be successfully performed in the operating room when interference factors are properly addressed. In fact, hearing thresholds can be accurately estimated based on the outcomes of ABR conducted in the operating room under the right circumstances, for example, in the absence of middle ear effusion or surgical procedure involved. In addition, the degrees and the types of hearing loss can be determined in most of the cases. When myringotomy and tube placement are done prior to the ABR testing, follow-up hearing evaluation when the ear is cleared and healthy, either by behavioral tests or by ABR testing, is necessary to determine a patient's true hearing thresholds or to confirm the hearing loss established by the ABR results from the operating room. Caution should be taken when interpreting the ABR results from the operating room, and appropriate parental counseling must be provided. It has to be noted that there are times in which ABR test in the operating room is the only option to assess a child's hearing ability.


Background Exhaled carbon monoxide (COex) level is positively associated with tobacco smoking and exposure to smoke from biomass/coal burning. Relatively little is known about its determinants in China despite the population having a high prevalence of smoking and use of biomass/coal.Methods The China Kadoorie Biobank includes 512 000 participants aged 30-79 years recruited from 10 diverse regions. We used linear regression and logistic regression methods to assess the associations of COex level with smoking, exposures to indoor household air pollution and prevalent chronic respiratory conditions among never smokers, both overall and by seasons, regions and smoking status.Results The overall COex level (ppm) was much higher in current smokers than in never smokers . Among current smokers, it was higher among those who smoked more and inhaled more deeply. Among never smokers, mean COex was positively associated with levels of exposures to passive smoking and to biomass/coal burning, especially in rural areas and during winter. The odds ratios (OR) and 95% confidence interval (CI) of air flow obstruction (FEV1/FVC ratio <0.7) for never smokers with COex at 7–14 and ≥14 ppm, compared with those having COex <7, were 1.38 (1.31–1.45) and 1.65 (1.52–1.80), respectively (Ptrend <0.001). Prevalence of other self-reported chronic respiratory conditions was also higher among people with elevated COex (P <0.05).Conclusion In adult Chinese, COex can be used as a biomarker for assessing current smoking and overall exposure to indoor household air pollution in combination with questionnaires. All participants gave their written informed consent.1 and FVC was conducted using a hand-held spirometer .COex level was measured by a hand-held battery operated meter . The device also estimates blood carboxyhaemoglobin  level based on its high correlation with COex level.n = 106, 0.02% of whole study population), since these values may well reflect on-site data entry error. The cut-point of 7 ppm for COex was chosen to define abnormal levels of exposure to smoking and indoor household sources of CO. This was partly based on the sensitivity and specificity analyses of the collected COex data among current smokers who smoked on the day of collection and never smokers , although the study was not designed to define the COex cutoff value for smokers and never smokers.The present study excluded the participants with extreme values of COex level (exceed the range of 1–99 ppm) and those whose COex levels were measured earlier than 07:00 am and later than 10:59 pm  of COex concentrations were calculated using the linear least squares regression method. A logistic regression model was used to estimate the odds ratio (OR) of various respiratory conditions according to different levels of COex among never smokers, adjusting simultaneously for age at survey, sex, education and other potential confounding factors. All analyses were performed using SAS 9.2 software.Supplementary Figure S1, available as Supplementary data at IJE online), and it also varied slightly with the season, especially among men.The overall arithmetic mean (SD) COex level was 7.8 ppm (2.6) for men and 3.3 ppm (2.3) for women, and the overall geometric means were 7.2 and 3.1 ppm, respectively. Geometric mean COex level was somewhat higher in rural than in urban areas and decreased gradually with increasing age among men, but varied only slightly with age among women . Men witIn both sexes, current smokers were much more likely to have increased levels of COex than never smokers , with thOverall, smokers of manufactured cigarettes had higher mean COex levels than smokers of other forms of tobacco  . Among tSupplementary Table S1, available as Supplementary data at IJE online).Among never smokers, the proportion having a COex level ≥7 ppm was much higher in rural (24%) than in urban areas (9%) after adjusting for age at the baseline survey, time of day, season, gender and education. In rural areas, 40% of never smokers were exposed daily to passive smoking, 54% used coal or wood as fuel for cooking, 33% had no chimney in the kitchen, 61% had a stove burning slowly indoors all day long and 11% used coal or wood as fuel for heating in winter. The corresponding figures in urban areas were all substantially lower, being 30%, 5%, 12%, 5% and 2%, respectively. In both urban and rural areas the proportion having an elevated COex level increased with greater weekly duration of exposure to passive smoking . SimilarSupplementary Figure S2, available as Supplementary data at IJE online).Across the 10 study areas, there was about a 3-fold variation in mean COex level among male never smokers, and about a 4-fold variation among female never smokers, with, for both sexes, the highest mean COex levels seen in Henan  and the lowest in Sichuan (southwest China) . The reg1/FVC <0.7) at baseline. There was a strong positive association between COex level and the prevalence of various chronic respiratory symptoms or conditions (Ptrend <0.001). The positive association between COex and risk of chronic respiratory symptoms or conditions was observed in both urban and rural areas .Among never smokers, about 2% had reported having chronic respiratory symptoms and the proportions having a prior history of doctor-diagnosed tuberculosis or of emphysema/chronic bronchitis were 1.2% and 2.2%, respectively. Based on the measured lung function, 4.1% could be classified as having airflow obstruction  and coal are the main indoor household sources for elevated CO.,The daily temporal trends and seasonal variations in COex level in the present study were consistent with findings reported in previous studies.,,Despite the 3-fold difference in the mean COex level between smokers and never smokers, the mean level of measured COex in CKB participants was only about half of that seen in Western populations for both smokers (∼10 in CKB vs ∼20 ppm) and never smokers (∼4 in CKB vs ∼8 ppm).P <0.01). Whereas the association could be largely causal, it is also possible that individuals with impaired lung function may not be able to clear CO from their lungs as effectively. If these findings were confirmed in similar prospective analyses of disease incidence, it would help to establish the value of COex, despite its short half-life, as a simple and practical biomarker for assessing exposure to indoor air pollution and its relation to long-term health effects.Although elevated CO level has previously been shown to be associated with increased risk of myocardial infarction in smokers,In summary, the present study has provided the first large-scale evidence from China that the level of COex is, on average, much higher in smokers than in never smokers and that it also correlates strongly with the amount of tobacco smoked and the degree of inhalation. Routine measurement of COex should be considered in future epidemiological studies of smoking as well as in smoking cessation programmes in China. Given the widespread use of biomass and coal for cooking and heating in many parts of rural China and the potential adverse health consequences, it may be appropriate to use COex as a simple surrogate biomarker to assess the overall burden of the exposure from such sources and its contribution to related health consequences. Continuing follow-up of the present study participants will soon provide large-scale prospective evidence on the relevance of such measures to subsequent health outcomes.Supplementary data is available at IJE online.Kadoorie Charitable Foundation in Hong Kong; follow-up of the project during 2009–14 is supported by the Wellcome Trust in the UK (grant 088158/Z/09/Z), and the National Key Technology Research and Development Program in the 12th Five-Year Plan, Ministry of Science and Technology, China; the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) at Oxford University also receive core funding for the project from the UK Medical Research Council, the British Heart Foundation and Cancer Research UK.The baseline survey and first re-survey in China were supported by a research grant from the


Introduction. Noise as a common physical hazard may lead to noise-induced hearing loss, an irreversible but preventable disorder. Annual audiometric evaluations help detect changes in hearing status before clinically significant hearing loss develops. This study was designed to track hearing threshold changes during 2-year follow-up among tile and ceramic workers. Methods. This follow-up study was conducted on 555 workers . Subjects were divided into four groups according to the level of noise exposure. Hearing threshold in conventional audiometric frequencies was measured and standard threshold shift was calculated for each ear. Results. Hearing threshold was increased during 2 years of follow-up. Increased hearing threshold was most frequently observed at 4000, 6000, and 3000 Hz. Standard threshold shift was observed in 13 (2.34%), 49 (8.83%), 22 (3.96%), and 63 (11.35%) subjects in the first and second years of follow-up in the right and left ears, respectively. Conclusions. This study has documented a high incidence of noise-induced hearing loss in tile and ceramic workers that would put stress on the importance of using hearing protection devices. Noise is the most common physical hazard in the industrial workplaces. A report from the European Union mentions that about 28% of workers are exposed to noise level approximately between 85 and 90 dBA . The mosIn the industrial settings, when noise exceeds permissible levels, hearing conservation program should be started, which contains hearing evaluation and some other activities.In 1996 National Institute of Occupational Safety and Health (NIOSH) reported that about 30 million workers in USA are exposed to loud noise which can lead to hearing loss . It is eNIHL is typically a bilateral and symmetric hearing loss with a notch of the audiogram at 3, 4, or 6 kHz and a recovery at 8 kHz as the first sign , 10.Prevention of deafness and hearing impairment (PDH), a WHO program, is especially planned for developing countries due to lack of accurate population-based studies about the prevalence and causes of deafness and hearing loss –13. OccuStandard threshold shift (STS) is defined as a 10 dB or more change in average hearing threshold at 2000, 3000, and 4000 Hz. So, even if the audiogram is not abnormal, positive STS is important to find those workers susceptible to hazardous effects of noise on hearing .Annual audiometric evaluations help detect changes in hearing status before clinically significant hearing loss develops . RecentlHong found a prevalence of 60% for hearing loss among construction workers which was directly related to work experience. They found left ear to be more sensitive to noise. Workers who used hearing protection devices (HPDs) showed lower frequency of hearing loss than others. They did not find a typical notch at 4 or 6 kHz [In a large study in The Netherlands they assessed the effect of duration of noise and noise level on the frequency of NIHL and found that duration of exposure is more important in NIHL causation than noise level . In anotOther studies in different parts of the world have assessed occupational hearing loss in different industries . In each factory subjects were selected by simple random sampling from different jobs. Each factory had 14 different job titles including glazing, glaze-making, forming, ball mill, spray drying, mixing and grinding, packing and loading, mechanic, forklift driving, warehouse, firing, printing, service, and office. These 14 subgroups were merged to produce 4 major groups according to noise level. Group 1  = 86.4 dBA) includes glazing, glaze-making, forming, packing and loading, forklift driving, firing, printing, and service; group 2  includes mixing and grinding, ball mill, and spray drying; group 3  includes mechanics; and control group (noise level: lower than 75 dBA) includes warehouse and office workers.This was a follow-up study conducted on 594 workers from 5 tile and ceramic factories in Yazd, a central province of Iran. Factories were selected by simple random sampling from all tile and ceramic factories in Yazd .Noise level was extracted from the result of measurements routinely performed in the factories by industrial hygiene incorporations and was presented as time-weighted average (TWA) for an eight-hour shift.Audiometry was performed for the subjects  in an acoustic chamber meeting the criteria of ANSI 2004  after att-test, chi-square test, and ANOVA. A P value of less than 0.05 was taken as the level of significance. An informed consent was obtained from each participant. This study was approved by the ethics committee of Shahid Sadoughi University of Medical Sciences.Data was analyzed by SPSS (ver. 18) using Student's After considering exclusion criteria and subjects who were lost from follow-up, 555 tile and ceramic workers entered the study . Mean hearing threshold was measured at each audiometric frequency. Percentage of abnormal threshold in different frequencies in each ear is shown in A number of subjects showed STS after first and second year of follow-up. STS was observed in 13 (2.34%) and 49 (8.83%) subjects in the first and second years of follow-up in the right ear and in 22 (3.96%) and 63 (11.35%) subjects in the first and second years of follow-up in the left ear.Noise as a common physical exposure in many industrial workplaces may lead to various health effects, especially NIHL. In this study we evaluated hearing threshold shift in a 2-year follow-up among tile and ceramic workers. The population which we studied was a young population with exposure to continuous noise during their eight hour work shift. Most workers in different parts of tile factories are exposed to noise level higher than ACGIH  TLV , that is, 85 dBA. The exposure to noise was not significantly changed during two years of follow-up. To the best of knowledge, this was the first follow-up study for finding hearing loss trends in tile workers in our country. In other countries we could not find similar studies on tile and ceramic workers.In the factories which were evaluated in this study, Hearing Conservation Program (HCP) according to OSHA is installed but not completely, so annual noise monitoring and annual audiometric tests are mandatory for the workers, but hearing conservation devices are not used regularly and workers are not trained accordingly . The useHow the workers used HPD is also another important factor that affects the true exposure to noise which could not be evaluated in this study , 29.In this study, the workers were categorized according to the exposure to noise which was evaluated environmentally, so the real exposure of each worker is probably different from that of another worker in the same job .In the current study, although the mean hearing thresholds at all frequencies were in the normal range, a considerable number of workers suffered from NIHL, and its frequency was significantly increased during the follow-up period (after 2 years). We found that hearing loss was significantly higher in the workers exposed to noise than in the control group consistent with the findings of Neitzel et al.  and OlogHearing loss was most commonly seen at 4000 Hz consistent with many other previous studies . So in mLow audiometric frequencies were affected in a few subjects. It is known that low audiometric frequencies are less susceptible to noise and are affected later than high frequencies, and our study subjects were mostly young persons with work experience less than 15 years. We found that the hearing threshold was clearly increased during follow-up time at these frequencies and lower frequencies were approximately intact even after 2 years of follow-up. We found a higher prevalence of hearing loss in left ear than right ear consistent with Hong , Ross etWe found that about 3% and 10% of subjects suffered from STS after 1 and 2 years follow-up, respectively. The change in mean threshold of 3000, 4000, and 6000 Hz (frequencies most affected by noise) was significantly higher than STS which is measured by the change in mean threshold of 2000, 3000, and 4000 Hz.One of the typical early signs of NIHL is a V-shaped notch which is mostly seen at the most sensitive frequencies to noise  . We founThis study had some limitations: some workers were transformed to another job inside the factory during follow-up period, but we assessed them as the members of the previous job. The number of female workers was low so we could not compare the results between males and females. There were 14 job titles in the factories, but in order to analyze the data we assessed them in four groups, so the workers in each group were exposed to a range of noise level. The workers used HPDs irregularly, so we could not analyze the data regarding HPDs use.This study showed a high frequency of hearing loss in tile and ceramic workers in spite of the obligation by health systems to install hearing conservation program.


We emphasize the importance of considering a diagnosis of early acquired syphilis in sexually active adults, and review the ENT manifestations and treatment of acquired syphilis.A 41-year-old man with left side hearing impairment since childhood presented with sudden hearing loss in the right ear; mild imbalance and clinical features suggestive of secondary syphilis (skin rash) developed lately. The first choice of treatment in the ENT department was followed after initial favorable evolution by relapsed sudden hearing loss in the right ear, dizziness, vertigo, nausea, and vomiting and gait impairment. The correct diagnosis was made after multiple evaluations in ENT, neurology, dermatology and infectious diseases departments.Combined ENT and infectious diseases treatment resulted in only partial recovery of hearing in the right ear and complete absence of dizziness.With the exponential rise in syphilis cases in Romania, there has been a reemergence of presenting manifestations that had previously become rare. Early syphilis should be considered in all sexually active adults who present with deafness, as prompt diagnosis and treatment are crucial for maximum recovery.


Nardostachys jatamansi (NJ) attenuated cerulein-induced mild acute pancreatitis (AP). In the present study, we investigated the ability of NJ to ameliorate severe acute pancreatitis (SAP) induced by a choline-deficient diet supplemented with ethionine (CDE). An NJ extract was orally administered ad libitum via the water during administration of the CDE. After three days, the CDE was replaced with a normal diet. After four days of normal feeding the mice were sacrificed and the blood and pancreas were obtained for further investigation. NJ treatment reduced SAP-induced pancreatic damage, as shown by histology. NJ treatment also inhibited neutrophil infiltration into the pancreas. NJ also inhibited the secretion of digestive enzymes and cytokine production, and inhibited the activation of mitogen-activated protein kinases (MAPKs) in the SAP-challenged pancreas. These data suggest that NJ protects against pancreatic injury in CDE-induced SAP by deactivating MAPKs.Previously, we reported that  The mortality and morbidity of acute pancreatitis (AP) generally depend on the severity of the disease, however, the mechanisms regulating its severity are poorly understood. Numerous studies have investigated the processes that regulate the severity of AP using murine AP models . Mild edNardostachys jatamansi (NJ) is widely used as a bitter tonic and anti-spasmodic .Avidin-peroxidase, Tris-HCl, NaCl, hexadecyltrimethylammonium bromide, ethionine and tetramethylbenzidine were purchased from Sigma-Aldrich . Anti-mouse tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 antibodies and recombinant TNF-α, IL-1β and IL-6 were purchased from R&D Systems . Anti-phospho-extracellular signal-regulated kinases (ERK) 1/2, anti-phospho-c-Jun N-terminal kinases (JNK) and anti-phospho-p38 were purchased from Cell Signaling Technology . Anti-inhibitory κ-Bα (Iκ-Bα), ERK 1/2, JNK, p38 and β-actin antibodies were purchased from Santa Cruz Biotechnology Inc. .NJ was purchased from a standard commercial source . The herb identity was confirmed at the Korean drug test laboratory. The NJ was prepared by decocting 100 g of dried herb with 1 l of boiling distilled water for approximately 2 h. The aqueous extract was frozen at −80°C then freeze-dried to form a 6.59-g powder. The yield of the extract was 6.59%. The powder was then rehydrated with distilled water, filtered and the filtrates were stored at 4°C until use.ad libitum for seven days prior to random assignment to experimental groups. The mice were fed the choline/methionine-deficient diet  supplemented with 0.5% DL-ethionine for three days. To ensure equal exposure by all animals, the diet was replaced with fresh CDE every 24 h. Following CDE administration, animals were provided with a normal diet for four days in order to estimate the 7-day mortality rate. The mice were then sacrificed, and the blood and pancreas were obtained. The blood samples were used to determine serum amylase, lipase and cytokine levels. For histological examination and scoring, the entire pancreas was rapidly removed from each mouse and fixed in formalin. Three portions of each pancreas were stored at −80°C for later measurement of tissue myeloperoxidase (MPO) activity as an indicator of neutrophil sequestration and for real-time reverse-transcription polymerase chain reaction (RT-PCR) measurements. NJ was dissolved in saline, then administrated orally ad libitum via water for seven days. There was no significant difference in the consumption of saline and NJ-containing saline.All experiments were performed according to methods approved by the Animal Care Committee of Wonkwang University. Female C57BL/6 mice (aged 3–4 weeks) were purchased from Orient Bio . All animals were bred and housed in standard shoebox cages in a climate-controlled room with an ambient temperature of 23±2°C and a 12-h light-dark cycle. The animals were fed a standard laboratory diet and water The arterial blood samples were obtained 6 h after induction of pancreatitis for the measurement of serum amylase and lipase levels. The mice were anesthetized with an intraperitoneal injection of ketamine (80 mg/kg) and xylazine (4 mg/kg). Following anesthetization, blood was aspirated from the heart into a syringe. Serum amylase was measured using ADIVA 1650 . Serum lipase level was measured using a Cobas Mira apparatus .An ELISA for TNF-α, IL-1β and IL-6 (R&D Systems) was carried out in duplicate in 96-well plates  coated with 100 µl of anti-mouse TNF-α, IL-1β or IL-6 monoclonal antibodies (1.0 µg/ml) in phosphate-buffered saline (PBS) at pH 7.4 following an overnight incubation at 4°C. The plates were washed in PBS containing 0.05% Tween-20 and blocked with PBS containing 10% FBS for 2 h. After additional washes, the standards and serum were added to the plates and incubated at room temperature for 3 h. The wells were then washed and 0.2 µg/ml of biotinylated anti-mouse TNF-α, IL-1β or IL-6 was added to each well and incubated at room temperature for 1 h. The wells were washed, avidinperoxidase was added and the plates were incubated for 30 min at room temperature. The wells were washed again and 3,3′,5,5′-tetramethylbenzidine substrate was added. Color development was measured at 450 nm using an automated microplate ELISA reader. Standard curves were obtained for each sample by using serial dilutions of recombinant TNF-α, IL-1β and IL-6.HPRT. The forward, reverse and probe oligonucleotide primers for Multiplex Real-Time TaqMan PCR were as follows: mouse TNF-α , mouse IL-1β , mouse IL-6 .The mRNA transcripts were analyzed by RT-PCR in mouse pancreatic tissue. The total RNA was isolated from the mouse pancreata using TRIzol  and subjected to reverse transcription using SuperScript II RT (Invitrogen). TaqMan quantitative RT-PCR was performed using a LightCycler 2.0 system according to the manufacturer’s instructions . Each reaction was performed in triplicate and a control reaction (without reverse transcription) was performed. All samples were analyzed for expression of the gene of interest and the results were normalized to those of the housekeeping mRNA, hypoxanthine-guanine phosphoribosyltransferase (HPRT). Arbitrary expression units were calculated by dividing the expression of the gene of interest by that of 2SO4 and the absorbance was measured at 450 nm.Neutrophil sequestration in the pancreas was quantified by measuring tissue MPO activity. The tissue samples were thawed, homogenized in 20 mM phosphate buffer (pH 7.4) and centrifuged . The pellet was resuspended in 50 mM phosphate buffer (pH 6.0) containing 0.5% hexadecyltrimethylammonium bromide. The suspension was subjected to four cycles of freezing and thawing and was further disrupted by sonication for 40 sec. The sample was then centrifuged  and the supernatant was used for the MPO assay. The reaction mixture consisted of the supernatant, 1.6 mM tetramethylbenzidine, 80 mM sodium phosphate buffer (pH 5.4) and 0.3 mM hydrogen peroxide. This mixture was incubated at 37°C for 110 sec, the reaction was terminated with 2 mol/l HThe pancreatic tissues were retrieved from storage at −80°C and homogenized in RIPA lysis buffer. Whole-cell lysates were obtained by boiling the homogenates in sample buffer . Lysate proteins were then separated by 10% SDS-polyacrylamide gel electrophoresis and transferred to PVDF membranes. The membrane was blocked with 5% skimmed milk in PBS-Tween-20 for 1 h at room temperature and then incubated with anti-phospho-ERK 1/2, anti-phospho-JNK, anti-phospho-p38 and anti-Iκ-Bα antibodies. After four washes in PBS-Tween-20, the blot was incubated with the secondary antibody for 1 h. Antibody-specific proteins were visualized by an enhanced chemiluminesence detection system according to the manufacturer’s instructions (Amersham Corp.).The results are expressed as the mean ± SEM of independent experiments. Independent one-way ANOVAs were used to analyze the statistical significance of the results between or among groups. All statistical analyses were performed using SPSS version 10.0 statistical analysis software . P<0.05 was considered to indicate a statistically significant result.To examine the effect of NJ on the development and severity of AP, mice were co-treated with NJ (5 or 10 mg/ml) and CDE-induced SAP. The severity of CDE-induced pancreatitis was assessed by histological examination. Pancreatic sections obtained seven days after the onset of SAP  significantly reduced the serum levels of amylase and lipase .It has been reported that ILs and TNFs increase during AP ,8. ThereWe assessed the effect of NJ on the activation of NF-κB  and MAPKIn the present study, we investigated the protective effects of NJ on diet-induced SAP. NJ inhibited the CDE-induced pancreatic damage markedly and reduced the digestive enzyme secretion and cytokine productions significantly. NJ treatment also reduced MAPK activation in a dose-dependent manner. Our results show that NJ may be a candidate for the treatment of SAP.In In the present study, NJ treatment inhibited the pancreatic and serum IL-1β, IL-6 and TNF-α levels . The proNF-κB and MAPKs play key roles in regulating the cytokines involved in acute inflammatory pancreatic diseases ,16. The Our results indicate that NJ has protective effects on SAP by inhibiting MAPK pathways, thereby inhibiting TNF-α, IL-1β and IL-6 production. NJ treatment also reduced neutro-phil infiltration into the pancreas and reduced levels of serum enzymes. Our findings suggest that NJ may be a candidate for SAP treatment.