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OBJECTIVE: The overall objective in the study was to compare self-reported hearing based on a single question ("how good would you currently rate your hearing?") to measure hearing loss determined by audiometry in a cohort of adolescents. Prevalence of audiometrically measured hearing loss and frequencies of self-reported poor hearing as well as factors that have an impact on self-reported hearing were examined. DESIGN: Baseline and 5-year follow-up data of the Ohrkan study were used. Participants filled in a questionnaire and underwent audiometric measurements. STUDY SAMPLE: Data from 979 adolescents were analysed. Participants were 54.7% female and aged between 13 and 18 years at baseline and 17-21 years at 5-yr follow-up. RESULTS: The single question on self-reported hearing ability achieved a sensitivity of 41.9% and a positive predictive value of 7.1% at baseline. For the 5-yr follow-up, sensitivity was 40.0%, positive predictive value was 13.9%. Factors influencing self-reported poor hearing were gender, tinnitus, "muffled" ears after exposure to loud noise (e.g. after a concert) and low-frequency hearing loss. CONCLUSIONS: The single question about hearing ability used in the Ohrkan study is not sufficient to replace audiometry to detect hearing loss as defined in the study in adolescents.

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Human toxoplasmosis is a life-threatening disease caused by the apicomplexan parasite Toxoplasma gondii. Rapid replication of the tachyzoite is associated with symptomatic disease, while suppressed division of the bradyzoite is responsible for chronic disease. Here, we identified the T. gondii cell cycle mechanism, the G1 restriction checkpoint (R-point), that operates the switch between parasite growth and differentiation. Apicomplexans lack conventional R-point regulators, suggesting adaptation of alternative factors. We showed that Cdk-related G1 kinase TgCrk2 forms alternative complexes with atypical cyclins (TgCycP1, TgCycP2, and TgCyc5) in the rapidly dividing developmentally incompetent RH and slower dividing developmentally competent ME49 tachyzoites and bradyzoites. Examination of cyclins verified the correlation of cyclin expression with growth dependence and development capacity of RH and ME49 strains. We demonstrated that rapidly dividing RH tachyzoites were dependent on TgCycP1 expression, which interfered with bradyzoite differentiation. Using the conditional knockdown model, we established that TgCycP2 regulated G1 duration in the developmentally competent ME49 tachyzoites but not in the developmentally incompetent RH tachyzoites. We tested the functions of TgCycP2 and TgCyc5 in alkaline induced and spontaneous bradyzoite differentiation (rat embryonic brain cells) models. Based on functional and global gene expression analyses, we determined that TgCycP2 also regulated bradyzoite replication, while signal-induced TgCyc5 was critical for efficient tissue cyst maturation. In conclusion, we identified the central machinery of the T. gondii restriction checkpoint comprised of TgCrk2 kinase and three atypical T. gondii cyclins and demonstrated the independent roles of TgCycP1, TgCycP2, and TgCyc5 in parasite growth and development. IMPORTANCE Toxoplasma gondii is a virulent and abundant human pathogen that puts millions of silently infected people at risk of reactivation of the chronic disease. Encysted bradyzoites formed during the chronic stage are resistant to current therapies. Therefore, insights into the mechanism of tissue cyst formation and reactivation are major areas of investigation. The fact that rapidly dividing parasites differentiate poorly strongly suggests that there is a threshold of replication rate that must be crossed to be considered for differentiation. We discovered a cell cycle mechanism that controls the T. gondii growth-rest switch involved in the conversion of dividing tachyzoites into largely quiescent bradyzoites. This switch operates the T. gondii restriction checkpoint using a set of atypical and parasite-specific regulators. Importantly, the novel T. gondii R-point network was not present in the parasite's human and animal hosts, offering a wealth of new and parasite-specific drug targets to explore in the future.

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PURPOSE: The aim of this study was to analyze the association of total leisure noise exposure and hearing threshold shifts over 5 years among adolescents enrolled in the Ohrkan cohort study. METHOD: The Ohrkan cohort of 2,148 students aged 13-19 years was recruited from 2009 to 2011 and followed up 5 years later. Complete baseline and follow-up reports on exposure and outcome were available for 989 participants. Leisure noise exposure was assessed by questionnaires, and clinical audiometric examinations were performed. Two outcomes were defined: occurrence of the Niskar notch pattern and audiometry showing maximum hearing threshold values at 3, 4, and 6 kHz (both ears). Longitudinal analysis using generalized estimating equations was performed. RESULTS: High total leisure noise exposure, defined as an energy equivalent of a 40-hr week of > 85 dBA, was estimated for 32.7% of students at baseline and 63.8% at follow-up. A noise notch was observed in 1.1% of adolescents at baseline and 3.3% at follow-up. At baseline, the maximum measured threshold shift was 55 dB, which increased to 85 dB at the follow-up. Longitudinal analysis did not reveal an association between leisure noise exposure and hearing thresholds. Hearing threshold shifts or noise notches were associated with sex, school type, and time point of measurement. CONCLUSIONS: No relationship was found between leisure noise and hearing thresholds. Male adolescents and those attending secondary general schools, with graduation following completion of ninth or 10th grade, had a greater likelihood of developing hearing threshold shifts. Prevention programs should focus on these risk groups. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19233462.

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OBJECTIVE: Investigating determinants of total leisure noise (TLN) exposure among adolescents over 7.5 years and compensating for missing data due to loss to follow-up. DESIGN: In the OHRKAN cohort study, data were collected by questionnaires at four waves. TLN was calculated from self-reported duration spent participating in 18 leisure activities. High exposure was defined as exceeding 85 dB(A) of equivalent continuous average sound pressure level (SPL) during a 40-h week. Multiple imputation (MI) and generalised estimating equations (GEE) were used to analyse odds ratios (OR) of determinants of TLN exposure and compared to complete-case analysis. STUDY SAMPLE: Closed cohort of 2148 students enrolled in grade 9 of any school in Regensburg (Germany), recruited from 2009 to 2011. RESULTS: Up to 74% of adolescents had risky TLN exposure, depending on wave. The most significant sources were discotheques, portable listening devices (PLD) and stereo systems. Higher TLN exposure was associated with time point, education, single-parent households and gender. MI under MAR assumption changed results only slightly compared to complete-case analysis. CONCLUSIONS: Prevalence of risky TLN is high during adolescence. MI reinforced trends detected in former results of OHRKAN. Preventive measures should consider the main drivers of noise exposure including changes by age and high risks groups.

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OBJECTIVES: To investigate the association between total leisure noise exposure and intermittent tinnitus among young adults. DESIGN: Data were obtained from the Ohrkan study, an ongoing prospective cohort study conducted in South Germany since 2009. Information about exposure to impulse and leisure noise, tinnitus occurrences, sociodemographic variables, and self-rated hearing ability were analysed at four time points over a period of seven and a half years. STUDY SAMPLE: Participants of the Ohrkan cohort study, who provided data about the occurrence of tinnitus for all surveys (n = 1028). RESULTS: Intermittent tinnitus was reported in the majority of the sample (60%). The risk for intermittent tinnitus increased with higher sound pressure levels from exposure to leisure noise (full model (Odds Ratio, 95%CI): 80-<85dB(A): 1.41 [1.13-1.78], 85-<90dB(A): 1.73 [1.38-2.16], >90dB(A): 2.04 [1.59-2.61]). Visiting nightclubs was a major contributor to this relationship. Of the considered covariables, self-rated hearing as "poor", and growing up in a single-parent household were significantly associated with intermittent tinnitus. CONCLUSION: Intermittent tinnitus is very frequent among young adults and is associated with high levels of leisure noise exposure. To prevent intermittent tinnitus, reduced sound pressure levels and the use of hearing protection are necessary.

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The aim was to investigate leisure noise exposure and sociodemographic determinants of risky leisure noise exposure over five years in 2148 students visiting grade 9 of any school type in a German city from 2009-2011. Within the OHRKAN cohort study, leisure noise exposure was calculated from literature-retrieved sound pressure levels (SPLs) and self-reported duration of 18 leisure activities at baseline and two follow-ups. Risky exposure was defined as exceeding 85 dB(A) averaged over a 40-h-week. Determinants of risky total leisure noise (TLN) exposure and risky exposure to portable listening devices (PLDs) were investigated using generalised estimating equations (GEEs). Up to 73% of students exceeded noise levels of 85 dB(A) at some timepoint. The noise exposure and importance of different leisure activities changed with increasing age. Risky exposure to TLN and PLDs was associated with lower education, single parent households and being male. Risky PLD exposure was additionally associated with a migrant background. Current prevention measures for leisure noise exposure must be extended to at-risk groups. Besides enhancing campaigns in lower education schools, acoustical insulation in sports halls, noise warnings on tools or in videogames could address especially men. Migrants need education about healthy PLD use in their native language if necessary.

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The aim of this study was to quantify major and trace elements in the water, soil, and plants (Carya illionensis) in an agricultural area; and to determine the health risks associated with the walnuts ingestion by calculating the risk quotient. Samples of water, soil, tree leaves, and walnuts were collected; in total, 135 samples were analyzed. Physicochemical parameters were obtained in irrigation water and soil samples. Elemental measurements were performed in an ICP, -OES and -MS. In addition, the distribution coefficient (soil⁻water), transfer factor (soil⁻plant), and hazard quotient were evaluated. In the irrigation water, As, Cr, and Pb, showed concentrations above the maximum allowable limits. Likewise, high concentrations of As, Cr, Pb, and Sb were found in tree leave samples, indicating a possible tendency of hyperaccumulation of those elements. Furthermore, Cr concentrations in walnuts were high by far than the reference value (FAO/WHO). A possible competition between chemical congeners were detected from transfer factors. Although, Sb concentrations in walnuts were also high, and no legislation for it in fruits exists. The hazard risk quotient for Sb did indicate a potential health risk. Finally, it is important to consider that the health risk increases when exposure through consumption takes place over a prolonged period of time, even in low concentrations.

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The unusual cell cycles of Apicomplexa parasites are remarkably flexible with the ability to complete cytokinesis and karyokinesis coordinately or postpone cytokinesis for several rounds of chromosome replication, and are well recognized. Despite this surprising biology, the molecular machinery required to achieve this flexibility is largely unknown. In this study, we provide comprehensive experimental evidence that apicomplexan parasites utilize multiple Cdk-related kinases (Crks) to coordinate cell division. We determined that Toxoplasma gondii encodes seven atypical P-, H-, Y- and L- type cyclins and ten Crks to regulate cellular processes. We generated and analyzed conditional tet-OFF mutants for seven TgCrks and four TgCyclins that are expressed in the tachyzoite stage. These experiments demonstrated that TgCrk1, TgCrk2, TgCrk4 and TgCrk6, were required or essential for tachyzoite growth revealing a remarkable number of Crk factors that are necessary for parasite replication. G1 phase arrest resulted from the loss of cytoplasmic TgCrk2 that interacted with a P-type cyclin demonstrating that an atypical mechanism controls half the T. gondii cell cycle. We showed that T. gondii employs at least three TgCrks to complete mitosis. Novel kinases, TgCrk6 and TgCrk4 were required for spindle function and centrosome duplication, respectively, while TgCrk1 and its partner TgCycL were essential for daughter bud assembly. Intriguingly, mitotic kinases TgCrk4 and TgCrk6 did not interact with any cyclin tested and were instead dynamically expressed during mitosis indicating they may not require a cyclin timing mechanism. Altogether, our findings demonstrate that apicomplexan parasites utilize distinctive and complex mechanisms to coordinate their novel replicative cycles.

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OBJECTIVE: To describe personal music player (PMP) usage among adolescents, sociodemographic determinants and association with audiometric notches. DESIGN: Audiometric evaluation to assess hearing status, and standardized questionnaires to evaluate PMP listening behaviors, leisure noise exposures and self-reported hearing loss symptoms. Sociodemographic information was collected using a parent questionnaire. Noise exposure by PMP usage equivalent for a 40 h week was estimated based on self-reported volume and duration of use. STUDY SAMPLE: A total of 2143 students (54% females) attending 9th grade in Regensburg, Germany, during 2009 to 2011. RESULTS: Overall, 85% of the students reported using PMPs. Exposure level exceeded 80 dB(A) in approximately one third, and 85 dB(A) in one quarter, of those who used PMP. An audiometric notch was found in 2.3% of participants, but was not significantly associated with higher PMP exposure. CONCLUSIONS: PMP exposure above the occupational limits of 80 and 85 dB(A) set by the Directive 2003/10/EC may be a risk factor for developing noise-induced hearing loss. Educational measures to ameliorate high risk behaviors in PMP usage are needed, particularly for socially disadvantaged groups.

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BACKGROUND: Studies investigating leisure noise effect on extended high frequency hearing are insufficient and they have inconsistent results. The aim of this study was to investigate if extended high-frequency hearing threshold shift is related to audiometric notch, and if total leisure noise exposure is associated with extended high-frequency hearing threshold shift. MATERIALS AND METHODS: A questionnaire of the Ohrkan cohort study was used to collect information on demographics and leisure time activities. Conventional and extended high-frequency audiometry was performed. We did logistic regression between extended high-frequency hearing threshold shift and audiometric notch as well as between total leisure noise exposure and extended high-frequency hearing threshold shift. Potential confounders (sex, school type, and firecrackers) were included. RESULTS: Data from 278 participants (aged 18-23 years, 53.2% female) were analyzed. Associations between hearing threshold shift at 10, 11.2, 12.5, and 14 kHz with audiometric notch were observed with a higher prevalence of threshold shift at the four frequencies, compared to the notch. However, we found no associations between total leisure noise exposure and hearing threshold shift at any extended high frequency. CONCLUSION: This exploratory analysis suggests that while extended high-frequency hearing threshold shifts are not related to total leisure noise exposure, they are strongly associated with audiometric notch. This leads us to further explore the hypothesis that extended high-frequency threshold shift might be indicative of the appearance of audiometric notch at a later time point, which can be investigated in the future follow-ups of the Ohrkan cohort.

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CONTEXT: Distortion product otoacoustic emissions (DPOAEs) may indicate preclinical noise-induced hearing loss (NIHL) in adolescents from unsafe personal music player (PMP) use. AIMS: The objective, therefore, was to observe preclinical signs of NIHL in 9th grade adolescents with clinically normal hearing by comparing DPOAE signals between different levels of A-weighted equivalent PMP exposure. SETTINGS AND DESIGN: Subjects were recruited from all secondary-level schools located in the city of Regensburg, Germany during two academic years 2009/2010 and 2010/2011. SUBJECTS AND METHODS: A-weighted equivalent sound pressure levels (SPLs) for a 40-hour work week (LAeq,40h) were estimated from questionnaire responses on output and duration of PMP use of the previous week. Subjects were then categorized into four levels of exposure: <80, 80-85, >85 to <90, and ≥90 A-weighted Decibel [dB(A)]. DPOAE signals were collected by trained audiological staff, applying a standard optimized protocol, at the Department of Otorhinolaryngology of the University Hospital Regensburg. STATISTICAL ANALYSIS USED: Mean DPOAE signals were compared between levels by unpaired t test. Novel linear regression models adjusting for other leisure noise exposures and with outcome variables DPoutcome and 4 kilo Hertz (kHz) DPOAEs estimated effects between levels. RESULTS: A total of 1468 subjects (56% female, mostly aged 15 or 16 years) were available for analysis. Comparison of DPOAE means by PMP exposure typically showed no greater than 1 dB difference between groups. In fact, comparisons between ≥90 dB(A) and <80 dB(A) presented the least differences in magnitude. Both DPoutcome and 4 kHz linear regression models presented a weak association with the 4-level PMP exposure variable. An expected dose-response to PMP exposure was not observed in any analyses. CONCLUSIONS: DPOAE signal strength alone cannot indicate preclinical NIHL in adolescents.

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Determining ionizing radiation in a geographic area serves to assess its effects on a population's health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h(-1). At the same sites, 48 soil samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and (40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h(-1). Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg(-1), for (226)Ra, (232)Th and (40)K, respectively. From the analysis, the spatial distribution of (232)Th, (226)Ra and (40)K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

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OBJECTIVE: To investigate total leisure noise exposure among adolescents and to assess its association with hearing. DESIGN: Based on self-reported time spent on 19 leisure activities and associated mean sound pressure levels reported in the literature, total leisure noise exposure was evaluated and compared to noise at work limits (> 85 dB(A) = hazardous) in a cross-sectional survey. Tympanometry and pure-tone audiometry was performed in sound isolated rooms. STUDY SAMPLE: The study sample consists of 2143 pupils attending grade nine in any school in a German city 2009-2011 (mean age: 15.4 years; range: 13-19 years). Audiometric data were available for 1837 (85.8%) pupils (53.9% girls). RESULTS: 41.9% of the 2143 adolescents who had provided self-reported data on leisure activities associated with noise exposure were estimated to be hazardously exposed to leisure time noise. The interaction of gender with total leisure time noise exposure was not significant. No association between leisure time noise exposure and audiometric notches could be detected. CONCLUSION: While hearing loss seems seldom in this age group, a high proportion of adolescents aged 15-16 years are exposed to noise levels during leisure time bearing long-term risks of hearing loss.

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Although there is concern about increasing hearing loss in adolescents caused by leisure noise exposure, prevalence data are scarce. In an US study, about 16-17% of adolescents were affected by audiometric notches. To estimate the prevalence of audiometric notches in adolescents in Germany, baseline data of the cohort study Ohrkan, recruitment during the school years 2009/2010 and 2010/2011 were analyzed. All students in grade 9 visiting any school in the city of Regensburg were eligible for participation. Data was collected via standardized questionnaires from students and their parents. In addition, students were asked to visit the University Clinics of Regensburg for ear examination including a tympanogram and the determination of hearing thresholds in air conduction audiometry. The prevalence of audiometric notches was determined in students with normal tympanogram in both ears and complete audiometry data. Audiometric notches were defined according to criteria used to analyse US data. Overall, 2149 students (1158 girls, 991 boys mainly aged 15-16 years) of the 3846 eligible adolescents (56%) participated. Among the 1843 adolescents with complete audiometry and tympanometry data, the prevalence of audiometric notches was 2.4% (95% confidence interval 1.7-3.1%). We could not confirm the high prevalence of audiometric notches as reported in National Health and Nutrition Examination Surveys for adolescents in the US. Differences in prevalence might be at least partly due to methodical differences in audiometry. Even if empirical evidence is presently ambiguous, it is reasonable to educate young people about the potential risks of high leisure noise exposure.

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Apicomplexa division involves several distinct phases shared with other eukaryote cell cycles including a gap period (G1) prior to chromosome synthesis, although how progression through the parasite cell cycle is controlled is not understood. Here we describe a cell cycle mutant that reversibly arrests in the G1 phase. The defect in this mutant was mapped by genetic complementation to a gene encoding a novel AAA-ATPase/CDC48 family member called TgNoAP1. TgNoAP1 is tightly regulated and expressed in the nucleolus during the G1/S phases. A tyrosine to a cysteine change upstream of the second AAA+ domain in the temperature sensitive TgNoAP1 allele leads to conditional protein instability, which is responsible for rapid cell cycle arrest and a primary defect in 28S rRNA processing as confirmed by knock-in of the mutation back into the parent genome. The interaction of TgNoAP1 with factors of the snoRNP and R2TP complexes indicates this protein has a role in pre-rRNA processing. This is a novel role for a cdc48-related chaperone protein and indicates that TgNoAP1 may be part of a dynamic mechanism that senses the health of the parasite protein machinery at the initial steps of ribosome biogenesis and conveys that information to the parasite cell cycle checkpoint controls.

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BACKGROUND: Injection laryngoplasty is an option for treatment of dysphonia following vocal fold paralysis. Modified fibrin glue with suspended chondrocytes might be a favorable cell-based material for permanent vocal fold medialization. METHODS: We compared fibrin glue with suspended chondrocytes to collagen and hyaluronic acid gels concerning alteration of vocal fold vibration and correct intralaryngeal placement after intralaryngeal injection into porcine larynges. Viscoelastic properties of the materials were analyzed by means of a parallel plate rheometer. RESULTS: Fibrin glue with cells was comparable to collagen and hyaluronic acid with respect to amplitudes, symmetry, and periodicity of vocal fold vibration. Application and positioning of fibrin glue with suspended chondrocytes were technically undemanding and comparable with controls. Complex stress modulus of fibrin glue with suspended cells was comparable to that of collagen gel. CONCLUSIONS: Fibrin glue with suspended chondrocytes seems suitable for the indication of injection laryngoplasty and holds promise for permanent vocal fold medialization.

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Se presenta una nueva observación de estenosis biliar poshidática con las siguientes particularidades: a.Complicación por absceso angiolítico en segmento hepático VI, que fue tratado y curado mediante drenaje transparietohepático directo, bajo control de imagen tomográfica. b.Estenosis incompleta de ambas ramas del hepático derecho, con mayor grado de la rama lateral determinando aquella angiocolitis y aquel absceso. c.Pérdida de sustancia del conducto izquierdo, cuyo extremo proximal se presenta estenosado y en comunicación persistente con la cavidad hidática residual. Comparando este ejemplo con otras observaciones del mismo tipo, establecemos las características de las lesiones controlaterales que se asocian a la estenosis ductal incompleta, principal responsable de los fenómenos patológicos. Los documentos colangiográficos son muy demostrativos de la afección, y con su auxilio se logró cateterizar la estenosis principal y dilatarla convenientemente. Se insiste en la necesidad de tener este problema presente y tratar de resolverlo en el momento inicial de abordar un quiste hidático central abierto en la confluencia biliar

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