Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n = 135) and controls (n = 443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS Gender role behavior is closely related to a person’s gender identity, denoting the extent of experience of conformity to others of the same gender or the sense of being a male or female1. Gender Dysphoria (GD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), refers to the conflict between a person’s assigned gender and the gender with which they identify2. The condition reflects the discomfort with the expected roles or the physical appearance that the assigned gender implies3.An individual’s sex at birth is determined based on genital appearance and is usually referred to as The use of psychometric instruments in transgender persons who seek healthcare for gender affirming treatment is often included in the evaluation process. The purpose of the use is partly as a diagnostic aid and partly as a baseline measurement for follow-up in the future.5. The scale has been reported to be able to distinguish between transsexual and non-transsexual persons as well as those suitable for gender affirming surgery4.The Utrecht Gender Dysphoria Scale (UGDS) was introduced around 1997 and GD is treated as being caused by the divergence between sense of self-gender identity and body aspects6 with a different approach. Authors aimed to capture somatic, sociolegal, social, and subjective dysphoria indicators. A person’s gender identity was treated as a bipolar continuum, with unproblematic gender identity and gender dysphoria being on the edges of the gender identity.The Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA) is a binary scale developed by Deogracias et al.7. The scale was designed to approach gender identity through the scope of the transgender model, which does not pathologize transgender individuals’ experiences and perceptions, as opposed to previous scales, that utilized the transsexual model. In the transgender model, gender is more fluid and changeable, rather than binary, and thus more inclusive7. Moreover, the TCS can be utilized for the evaluation of patients that do not undergo both hormonal and surgical gender affirming treatment while the UGDS and GIDYQ scales lack this option because they comprise questions on specific sex characteristics. For these reasons, the non-binary character of the TCS scale can be applied to individuals before and after different modalities of gender affirming treatment as well as to persons with non-binary gender identity. Validation of the TCS scale could promote the use of this non-binary, short and easy to administrate scale in the context of clinical evaluation and prediction of outcomes in transgender people.The Transgender Congruence Scale (TCS) was developed by Kozee et al. in an attempt to capture the transgender’s congruence with their own gender identity perceptionThe aim of this study was to evaluate the psychometric properties of TCS and its capacity to distinguish individuals with gender dysphoria in the Swedish setting. A secondary aim was to examine the scale’s concurrent validity by comparing TCS with two more widespread and better-validated scales, the UGDS and the GIDYQ-AA.The present project is part of the Swedish Gender Dysphoria Study , an ongoing longitudinal multicenter study on gender dysphoria. SKDS aims to investigate how anamnestic, socio-demographic, biological, neurocognitive, and personality-related factors affect physical and mental health, social integration and quality of life in people with GD.The SKDS study was initiated in 2016. All individuals with an ongoing health-care contact within psychiatry, endocrinology or gynecology for gender dysphoria evaluation or treatment at one of the participating centers in Alingsås/Gothenburg, Linköping, Lund/Malmö, Stockholm, Umeå and Uppsala are being asked about participation in SKDS. Exclusion criteria are age < 15 and inability to adequately communicate in Swedish. All potential participants receive oral and written information as well as a prepaid envelope and a form for obtaining consent. The recruitment rate of the SKDS study is 77%.Study controls were recruited via email-based open invitations to medical students in Uppsala University as well as students in psychology, the Bachelor’s programme in personnel, work and organization and the psychology programs 1, 2 and 3 at Stockholm University. Additional recruitment was utilized with posters at university facilities, the public library and on social media (Facebook).Questions on gender dysphoria topics that were not relevant for controls were excluded from the surveys or replaced with the question “have you been treated for gender affirming purposes now or in the past?”. Respondents that were diagnosed with GD or had undergone gender affirming treatment as well as those with answers that implied gender dysphoria were excluded from the control group.Psychometric instruments  were distributed during the second week after inclusion in both groups. The sex-specific UGDS and GIDYQ-AA version was determined from the answer on the birth-assigned sex question. In the case group, all participants were administered the TCS scale and either the UGDS or the GIDYQ-AA scale. In the control group, all participants received all three rating scales. For the TCS and UGDS scales, up to two missing answers were accepted in order to be included in the analyses, while the corresponding number for the GIDYQ-AA was five questions.Until April 2019, 328 patients were recruited in the SKDS study. Of those, 90 were aM, 142 were aF and data on birth-assigned sex was missing for 96 persons who were therefore excluded from the present study. Furthermore, 80 persons  had started hormonal treatment and were excluded due to the possible effect of the treatment on GD scales evaluation. Five individuals  with missing data on this question were also excluded from the study sample. Finally, we excluded from further analyses individuals where no TCS data was available (2 aM and 7 aF) as well as those that had missing answers in > 2 statements in TCS . Finally, one aF had nine missing answers in GIDYQ-AA and was thus excluded. Therefore, the group of patients with GD consisted of 135 study participants .In the control group, 561 individuals responded to the invitations and no data on birth-assigned sex was available for two persons who were thus excluded. Of the remaining 166 aM and 393 aF, 13 persons reported a legal sex different from their birth-assigned sex and were therefore also excluded. Furthermore, we excluded 11 individuals  that reported previous gender affirming treatment, and one more person with missing relevant data. An additional subgroup of 29 persons was excluded due to self-reported diagnosis of GD (1 aF), unspecified gender identity disorder  or ongoing GD investigation . Furthermore, 12 individuals that expressed a wish for legal sex reassignment were not included in the final study sample. Finally, one aF with multiple missing answers on TCS as well as 47 persons  lacking data on the whole TCS scale were also excluded. After excluding one aF with missing answers on seven items in UGDS, 443 study participants comprised the control group.Ethical approval regarding patients with GD was obtained from the Regional Ethical Review Board in Uppsala . Data on controls were anonymous; therefore, no ethical approval was necessary for this group. All research was performed in accordance with relevant guidelines and regulations. Informed consent was obtained from all participants.8. To date, there are no published studies on the performance of UGDS in a Swedish setting, but preliminary unpublished data from our group suggests good psychometric properties when validated against the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA) .The UGDS scale is binary; hence existing in two difference versions, one for aM and the other for aF persons. It consists of 12 items with answers on a five-point Likert-type scale (points 1–5 per item) and focuses on gender identity and roles as well as body aspects. A higher point sum indicates GD and a threshold of 50 to 60 points has been suggested as indicative of severe GD6. The scale has been validated by Singh et al. with excellent sensitivity and specificity figures9. The performance of GIDYQ-AA in a Swedish setting has been only validated by unpublished work .The GIDYQ-AA scale consists of 27 questions with five-point Likert-type possible answers , for the previous 12 months, and a lower calculated mean value points towards GD. Two different versions for aM and aF exist. As reported by the authors, a threshold of three points would have a 90.4% sensitivity and 99.7% specificity to identify GD appearance congruence (statements 1–9), examining whether external appearance adequately represents gender identity, and gender identity acceptance (statements 10–12), which reflects the extent of perceived gender identity acceptance as opposed to the assigned by the society gender identity. A low mean score is associated with higher symptoms of GD. To meet the need for a validated instrument that can evaluate treatment results in persons who have undergone different kinds of gender affirming surgery in Sweden, the TCS scale was translated following the World Health Organization’s recommendations10, after permission from the authors. Thereafter, the scale was tested in 26 persons in various phases of evaluation and treatment where the majority of participants perceived the scale as non-binary and easy to complete11.The TCS scale consists of 12 statements about the past two weeks with five Likert-type possible answers (1–5 points per statement). The scale measures two factors: Participants were asked about their education level (dichotomized as primary school/high school vs. university/college) and occupation . Satisfaction with body appearance was measured on a 100-point Likert-type scale , as did gender incongruence . Furthermore, participants were asked about their sexual orientation  and categorized as androphilic (attracted only/mostly to men), gynephilic (attracted only/mostly to women) or bisexual .U-test was applied.Univariate differences in sociodemographic data between patients with GD and controls were examined by use of chi-square test for binary variables. The satisfaction with body appearance and gender incongruence scores were not normally distributed (Kolmogorov–Smirnov and Shapiro–Wilk tests). Thus, the non-parametric Mann–Whitney For each respondent, a TCS and GIDYQ-AA mean score was calculated, where lower mean value suggests stronger gender dysphoria. Regarding UGDS, scores were instead summed up, higher sum being indicative of gender dysphoria. The questions with a reverse score were inverted before calculating response points.12. A confirmatory factor analysis (CFA) was performed to test the construct validity of the TCS instrument for the total study sample. Due to ordinal data structure, the DWLS  estimator was used. Comparative Fit Index (CFI), Standardized Root Mean Square Residual (SRMR) and Root Mean Square Error of Approximation (RMSEA) were used as model fit indices. CFI ≥ 0.95, SRMR < 0.08 and RMSEA < 0.06 were considered as an indication of good fit13.To calculate the internal consistency of the TCS scale, McDonald’s ω was used14.To evaluate the factor structure of the TCS scale across subgroups, two multiple-group confirmatory factor analyses (MGCFA) with mean structures in order were executed. Birth-assigned sex as well as patients with GD and controls were used as subgroups. For each MGCFA, we started with no constraints on factor loadings or item intercepts, which served as the baseline model. Next, we ran the MGCFA with factor loadings constrained to equality. In a third step we constrained the item intercepts to equality. Due to inequality in sample sizes, ΔCFI < 0.01 and ΔRMSEA < 0.015 were used when comparing changes in model fit indicesappearance congruence and gender identity acceptance factors and for each TCS question), as well as UGDS and GIDYQ-AA scores, between patients with GD and controls, was performed separately for aM and aF with Mann–Whitney U-test, since the scales’ scores did not follow a normal distribution, neither in the total study sample nor within patients with GD and controls (Kolmogorov–Smirnov and Shapiro–Wilk tests). Moreover, differences in TCS scores between patients with GD and control subgroups, based on sexual orientation and stratified by birth-assigned sex, were examined with Kruskal–Wallis test, as it has been previously observed that homosexual controls (based on birth-assigned sex) demonstrate higher symptoms of gender dysphoria on GD evaluation scales.Comparison of TCS scores  curves were constructed and sensitivity and specificity values were calculated for different TCS thresholds, separately for each birth-assigned sex. Correlations between TCS and its factors with UGDS and GIDYQ-AA were examined with Spearman’s ρ.p < 0.05. Internal consistency, confirmatory factor analysis and multiple-group confirmatory factor analysis were calculated with R version 3.5.1. The Statistical Package for the Social Sciences (IBM SPSS Statistics) version 25 was used for all other analyses.Statistical significance was set at 2 derived p = 0.089). Due to the recruitment approach of the control group through universities, education level in this group was significantly higher, compared to patients with GD . Furthermore, groups differed significantly in age and occupation status and, as expected, in satisfaction with body appearance  = − 0.66) and gender incongruence .Sociodemographic data is presented in Table appearance congruence factor and 0.784 for the gender identity acceptance factor. Regarding the total study population, confirmatory factor analysis supported the two-factor model of the TCS scale, where all questions loaded strongly on their factors. CFI was 0.974, SRMR 0.022 and RMSEA 0.049, indicating a good fit between the model and the observed data. Standardized factor loadings are provided in Table The internal consistency of the TCS scale was analyzed with McDonald’s ω, which was 0.962 for the total scale, 0.985 for the 2 [df = 106] = 565.85, CFI = 0.954 and RMSEA = 0.093), indicating configural invariance (similar factor structure for aM and aF). Next, we fixed the factor loadings to equality across aM and aF , which indicated metric invariance (similar factor loadings for aM and aF) since CFI changed < 0.01 and RMSEA changed < 0.015 compared to the baseline model. Finally, we fixed the intercepts to equality across aM and aF and this model  indicated scalar invariance (similar item intercepts for aM and aF) since CFI changed < 0.01 and RMSEA changed < 0.015 compared to the previous model. When running MGCFA for patients with GD and controls in the same way, the baseline model had adequate fit , indicating configural invariance. Thereafter, the factor loadings were fixed to equality across aM and aF . Since CFI changed > 0.01 compared to the baseline model the criterion of metric invariance was not fulfilled.Regarding MGCFA for birth-assigned sex, the baseline model, which freely estimated factor loadings and intercepts across birth-assigned sex, had adequate fit  and gender identity acceptance  as well as when comparing each TCS question separately. Patients with GD had significantly lower scores in all 12 TCS items compared to controls, except for question 10 in aM . Similar results were observed regarding the UGDS  and the GIDYQ-AA . Results of the analyses named above remained unaltered after stratifying for sexual orientation  and GIDYQ-AA  Table .Table 6Sappearance congruence and gender identity acceptance, in both birth-assigned sexes. TCS had also high concurrent validity when compared to the UGDS and GIDYQ-AA.Results of the present study provide evidence that the Swedish version of TCS is a non-binary scale with good psychometric properties and can distinguish individuals with gender dysphoria. The scale had sound discriminatory qualities as a whole and even in its separate factors of 6. In our study, the only significant difference in terms of gender dysphoria symptoms, among sexual orientation control subgroups, was observed between androphilic and bisexual female controls, where bisexuals scored lower on TCS. However, the difference in median TCS scores between these two groups was only 0.33 points, while the overall TCS median score among controls was at least twice as high as for patients with GD. Therefore, the present data do not support the need of considering sexual orientation when evaluating gender dysphoria with the TCS scale.It has previously been reported that non-heterosexual men and women, defined on the basis of birth-assigned sex, may exhibit significantly more gender dysphoria than heterosexual individuals7. Multiple-group confirmatory factor analysis suggested measurement invariance between birth-assigned sexes. Only configural invariance was shown between patients with GD and controls. When checking for metric invariance between patients with GD and controls, the decrease in CFI can possibly be explained by the fact that the TCS was constructed to detect GD and is thus more fitted for individuals with symptoms of gender dysphoria.Confirmatory factor analysis supported the two-factor model, in accordance to the original TCS studySensitivity and specificity cut-off values were similar between birth-assigned sexes, since a TCS mean value between 3 and 3.29 yielded a sensitivity of 94.3–98.1% and a specificity of 98.6–95.7% for aM, while for aF the corresponding values were 95.1–100% for sensitivity and 98–96.1% for specificity, for the same TCS cut-offs. These results further support the notion of TCS as a non-binary and sex-independent scale for assessing gender dysphoria, even if we did not explicitly study the validity of the scale in non-binary persons.https://konsdysforiregistret.se/). Moreover, it has been shown that patients perceive less distress, greater satisfaction with their body and better mental health and life satisfaction after gender affirming surgery15. Therefore, instruments that assess satisfaction, quality of life and body perception are needed, in order to evaluate treatment results and properly follow-up transgender individuals, as described in a systematic review by Barone et al.16. In fact, the research group that constructed the TCS suggests its use in various time-points during the course of treatment, as a measure of within-individual congruence changes7. Further studies should investigate the scale’s function in terms of following up treatment effect and patient satisfaction.This study provides supportive evidence for using the scale in clinical practice in the Swedish gender dysphoria evaluation centers. A large proportion of transgender people seeking care in these clinics are interested in gender affirming hormonal therapy and some sort of surgery . Before the development of TCS we lacked an instrument that could assess treatment results in persons that had undergone some but not all gender affirming treatments, since the UGDS and the GIDYQ are problematic in these cases. TCS has increasingly been used by clinicians who assess patient with GD in Sweden and is also included as a Patient Reported Outcome Measure (PROM) in the national quality register for gender dysphoria  which includes measurement of gender congruence, mental health and quality of life and has similar advantages with the TCS, but the Swedish version of the scale has not yet been validatedThis is the first study to validate the Swedish version of the TCS in transgender individuals seeking healthcare. Although the sample size on which the development of the TCS tool was based on was larger, the present study still had a reasonable number of participants with probable gender dysphoria recruited from various GD evaluation centers as well as a large control group. The high recruitment rate and the relatively large amount of available background data of study participants should be considered as study strengths.18. On the other hand, the study sample assessed upon construction of the TCS scale was also older7, implying that the scale fits groups of various age ranges. Furthermore, it has been reported that the number of young participants seeking care in gender dysphoria centers has gradually increased over time19.Study groups were quite homogeneous by implementing exclusion of transgender people on hormonal treatment as well as controls that reported gender affirming treatment or the wish for it. This should have counterbalanced the over-representation of gender dysphoric controls that were willing to enroll to the study, since it seems plausible that these individuals may have been more interested in participating in the study. However, this aspect should still be considered as a study limitation. Nevertheless, a possible misclassification towards this direction should only have debilitated the observed significant differences between study groups. Study results should be interpreted with caution, in terms of study generalizability, considering the rather young study sample in both groups. Indeed, the vast majority of participants were younger than 40, while other studies in Sweden report older study samples of individuals applying for gender affirming medical treatmentThe significantly higher proportion of controls with higher education depends mainly on the recruitment strategy as well as study setting, since Uppsala inhabitants generally have a higher educational level, compared to the Swedish population in general.Another study limitation is the lack of gender dysphoria diagnosis upon enrollment of patients with GD. According to the DSM-5 definition, gender dysphoria criteria should last for at least six months. However, almost all patients initiating a gender dysphoria evaluation in one of the centers can be considered having major gender dysphoria symptoms even if they do not fulfill the diagnostic criteria. Moreover, the average waiting time for initiation of evaluation in a gender dysphoria center in Sweden is approximately one year, which suggests that these symptoms are persistent over time. Finally, in this study we did not have data on self-reported non-binary identification, which would allow us to specifically evaluate the function of the scale in this population.In this study, the Swedish version of the Transgender Congruence Scale has been validated in transgender individuals seeking healthcare in gender dysphoria evaluation centers. TCS had good psychometric properties and could distinguish individuals with gender dysphoria, in both birth-assigned sexes. A TCS mean score with a cutoff of 3.0 is suggested for screening of GD among persons with gender dysphoria symptoms. More research is warranted for the utility of the scale during the follow-up of patients receiving gender affirming treatment, as the sex-independent structure of the scale is well suited for this purpose.


Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential. Long-term noise exposure can result in sensorineural deafness commonly called noise induced hearing loss (NIHL). The phantom auditory sensation, tinnitus, can also result from noise exposure, although understanding of the underlying pathophysiology of tinnitus has been limited to date. According to the World Health Organization, in 2020 about 466 million individuals worldwide have disabling hearing loss, which is expected to almost double by 2050; about 34 million children have hearing loss; and up to 60% of cases are preventable . Among tPermanent hearing loss may develop as a result of noise exceeding 89 dB A for more than five hours a week . Other fThis review explores questions about the early signs of hearing difficulties, links between tinnitus and noise exposure, the preventability of NIHL, possible reversal of sensorineural hearing damage, detection of so-called ‘hidden’ hearing loss, developments in assessment and detection, appropriate prevention plans, adaptation of the central auditory system to changes, and treatments in development.Extended exposure to noise can result in continuous apoptosis of hair cells and degeneration of spiral ganglion neurons, gradually decreasing speech recognition and increasing hearing thresholds, which can lead to permanent hearing loss . At the Audiograms confirming hearing loss have long been recognized as the most important condition predisposing individuals to tinnitus ,27. StudAnimal models have contributed important information to the study of NIHL. In animals hearing loss after exposures of only 24 h can damage sensory hair cells in the inner ear . TinnituSeveral recent review studies have emphasized the maladaptive plasticity of NIHL, covering detailed neuronal aspects of triggers of tinnitus, mechanisms underlying generation of tinnitus in the cochlear nucleus after noise-induced deafferentation, likely routes of transmission of tinnitus signals along the ascending nuclei, as well as treatment approaches to reduce the impact of tinnitus on the quality of life of affected individuals ,37,38,39Most current audiological assessments are noninvasive and focus on peripherally presented sounds, measuring the individual’s ability to hear different frequencies. Pure-tone audiometry identifies an individual’s hearing threshold and can determine the degree, type and configuration of hearing loss as a basis for diagnosis and subsequent management. It is used effectively for threshold audiometry and screening, with 92% sensitivity and 94% specificity in detection of sensorineural hearing impairment . More coRetro-cochlear screening is typically performed when hearing loss is sudden or progresses rapidly, or is an asymmetric sensorineural loss. This can involve auditory brainstem response testing and/or gadolinium-enhanced magnetic resonance imaging (MRI) to detect retro-cochlear pathology such as vestibular schwannomas, cerebellopontine angle tumors, multiple sclerosis or stroke, among other possibilities .Structural neuroimaging studies are increasingly being performed to evaluate the effects of hearing loss on the brain. MRI technology, in particular, is sensitive to the changes in white and gray matter structures and allows quantitative evaluation at the macroscopic level. Structural MRI can be combined with fMRI to provide brain mapping and biomarkers for tracking amplification longitudinally . DiffusiMore sophisticated laboratory studies are also being conducted to clarify central nervous system (CNS) involvement in hearing loss. Because auditory processing begins in the cochlea and the sounds detected by sensory hair cells are then transmitted to the CNS by multiple types of spiral ganglion neurons, hearing assessment sometimes targets the post-cochlear regions, including the CNS. The mechanically sensitive hair cells in the cochlea relay auditory information to the CNS by releasing glutamate to the spiral ganglion neurons (SGN). Different SGN subtypes have been identified in molecular studies and found to have different morphology, innervation patterns and firing characteristics . ElectroCurrent difficulties in clinical audiological assessment include the fact that some individuals with hearing thresholds within normal limits (= < 25 dB HL) still find it difficult to hear clearly in noisy environments. This condition is often referred to as “hidden hearing loss,” which differs distinctly from loss due to shifts in the hearing threshold. However, it should be appreciated that the 0 dB HL is the average hearing of young adults. Some people had thresholds of −10 dB HL when they were 21 years old. If their thresholds are 0 dB HL at the present, they now have a sensorineural hearing loss. Individuals who self-report tinnitus can also can have audiograms with thresholds of 25 dB HL or less. Tinnitus can be measured, focusing on its pitch, loudness and mask ability and using a variety of magnitude estimation procedures ,48. The Gap-prepulse inhibition of the acoustic startle reflex (GPIAS) is reserved for tinnitus evaluation, particularly in animal models of tinnitus . The tesAn overall goal of assessment is to detect early hearing problems in a timely manner so that steps can be taken to prevent further damage. Auditory assessment, therefore, must consider the early transient changes, including when and how various perceptual abnormalities begin to emerge—and, importantly, to do this before permanent hearing impairment occurs.Treatments are necessarily different when targeting hearing loss or tinnitus alone. Stem cell therapy, for example, targets mainly hearing loss, and stimulation of the vagus nerve targets mainly tinnitus. Here we review current treatment methods, including those commonly used for treatment of hearing loss and a separate subsection for “tinnitus management.”Although hearing aids have been the conventional solution to hearing loss associated with aging or noise exposure, surgically implanted electronic devices may be indicated for adults and children with profound sensorineural hearing loss. Although these cochlear implants have been used for thirty years, and usage increases steadily, improvement cannot be predicted easily. Speech perception can present challenges among recipients . Poor ouPharmacologic agents applied in the treatment of hearing loss include glutamate inhibitors such as caroverine (Tinnex), derivatives of trimetazidine anti-ischemic agent such as trimetazidine dihydrochloride (Adexor), and lidocaine perfusion of the inner ear specifically for tinnitus. These treatments are not available in all countries and reports of effectiveness are controversial ,57,58.The damage in NIHL involves mechanical shearing force, oxidative damage and glutamate excitotoxicity, any of which could be eventual targets for post-exposure treatment and prevention. However, avoiding noise remains the present reality in terms of agents of prevention.Animal studies show that antioxidant enzymes from the body’s biochemical pathways, especially glutathione, increase in the cochlea after noise exposure. Acting as an effective antioxidant, glutathione scavenges free radicals in the cochlea after noise exposure, and transcription of large quantities of antioxidant enzymes SOD1 and HO-1 genes also provides a certain protective effect . These oSince no cure is available for tinnitus, management usually requires a broad, comprehensive approach to therapy. Treatment typically includes counseling, hearing aids, and sound therapy . A varieResults of recent clinical trials on hearing loss evaluation, prevention and treatment are pointing the way beyond current practices and available screening and treatment strategies. The challenges are many, including the difficulties in choosing the subtypes of tinnitus and of focusing on individual differences in hearing loss ,67. HereIntensive research is directed toward protecting the sensory hair cells, the auditory neurons and the ribbon synapses connecting the hair cells, focusing primarily on gene and cell-based therapies ,68. GoalStem cell differentiation and regeneration of hair cells has been found promising; if regeneration of hair cells were possible, noise-induced hearing losses could be prevented or corrected entirely . DiffereExperimental studies targeting central auditory plasticity are one approach. For example, animal studies are targeting maladaptive plasticity in the brain regions of animals with tinnitus, either aiming to reverse the pathological neural activity representing phantom perception of sounds (vagus nerve stimulation (VNS) combined with sound stimulation to alter cortical plasticity) , or aimiIn a review by Shore et al. , alterinAlthough many pharmacological approaches have been investigated for treating tinnitus, none have produced consistent effects on tinnitus loudness . HoweverThe increasing trends in the incidence and prevalence of hearing loss are due in part to demographic changes such as global population growth, the increased proportion of older adults >age 65 years) and increased life expectancy . However5 years aAs awareness of the adverse effects of noise increases, healthcare providers are more often recommending personal hearing protection (PHP) and hearing protection devices (HPD); only about 8% of surveyed U.S. adults report using HPDs at loud sporting or entertainment events . Simple Workplace prevention plans for hearing loss are characteristically based on Occupational Safety and Health Act (OSHA)\ regulations that impose strict limits on noise exposure. A recent study exploring whether noise-induced cochlear neuropathy occurring in rodents may justify changes in OSHA regulations argued that (1) humans are less susceptible to temporary threshold shift and cochlear damage than rodents, and (2) exposures that cause cochlear damage in rodents already exceed OSHA limits . TherefoAll people are exposed to noise. However, while the pathogenesis of NIHL is complex, cochlear neuropathy is largely preventable. Advances in our understanding of neural plasticity and adaptive changes in the central auditory system suggest that reversing transient abnormalities when they first emerge may be possible, but ongoing research remains critical, particularly in the assessment and early detection of hearing difficulties before they become permanent. Results of animal and human studies are essential to improve our understanding of neural mechanisms underlying the generation of NIHL, and are critical for developing effective treatment and therapies. Studies must continue to investigate ways to reduce NIHL and improve the quality of life for those who have sustained such hearing impairment. Because no treatment is yet able to completely reverse cochlear damage, continual exploration of new treatments for hearing impairment, implementation of preventative strategies and awareness of hearing health is also crucial.


We aimed to compare the electrophysiology and magnetic resonance neurography (MRN) results of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) subtypes and to explore the progression from atypical CIDP to typical CIDP. We collected the medical records of 45 CIDP patients to analyse the rate of progression from atypical CIDP to typical CIDP subtypes. The cerebrospinal fluid (CSF) protein (p = 0.024) and overall disability sum score (ODSS) (p = 0.000) differed among patients with typical CIDP, distal acquired demyelinating symmetric neuropathy (DADS) and Lewis-Sumner syndrome (LSS). The compound motor action potential (CMAP) of typical CIDP was lower than that of the other subtypes . The cross-sectional area (CSA) of nerve roots in typical CIDP was significantly thicker than that of nerve roots in DADS and LSS. There were fewer DADS and LSS patients who progressed to typical CIDP than those who progressed to pure motor and pure sensory CIDP (p = 0.000), and the progression from pure motor to typical CIDP required a significantly longer time than the progression from pure sensory to typical CIDP (p = 0.007). Typical CIDP was more severe than the other subtypes not only in terms of clinical and electrophysiology factors but also in terms of MRN factors. CIDP was divided into typical and atypical CIDP by the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS)2. The clinical presentation of typical CIDP includes chronically progressive or recurrent symmetric proximal and distal weakness, sensory dysfunction, and absent or reduced tendon reflexes in all extremities3. Atypical CIDP is regarded as a clinical variant of CIDP and is classified into five subtypes according to various clinical symptoms: distal acquired demyelinating symmetric neuropathy (DADS), pure motor or sensory CIDP, Lewis-Sumner syndrome (LSS) and focal CIDP5. The different CIDP subtypes have different responses to treatment7.Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated disease that targets the myelin sheaths of peripheral nerves; this disease has a chronic course and often causes disabled sensory-motor neuropathy9. Another point that should be noted is that there is no clear boundary with delineated criteria for the diagnosis of atypical CIDP. For example, it is unclear whether CIDP should include patients with clinical manifestations of sensory impairments but both sensory and motor neuro-electromyography abnormalities or those only with clinical and electrophysiology sensory disturbances4.There is an interesting phenomenon regarding typical and atypical CIDP, where the diagnosis is not fixed but can change over time. For example, some patients may initially present with pure sensory, pure motor, or LSS that then evolves over a few months to a typical sensorimotor form12. The aim of our study is to prospectively explore the discrimination of typical CIDP from its variants according to electrophysiology and magnetic resonance neurography (MRN). At the same time, we retrospectively researched the features and frequencies of atypical CIDP conversion to typical CIDP.The different subtypes of CIDP have not only different clinical features and treatment responses but also diverse imaging and electrophysiology performancesA total of 32 typical CIDP patients , 6 DADS patients  and 5 LSS patients  underwent clinical, electrophysiological, and MRN evaluations. We only compared the data of typical CIDP, DASD and LSS patients because the number of pure motor and sensory CIDP patients was too low for the analysis. The demographic and baseline clinical data are presented in Table The CMAPs of the median nerves in DADS patients and the CMAPs of the tibial and peroneal nerves in LSS patients were all higher than those in typical CIDP patients . The SCVs of the median and ulnar nerves in LSS patients were slower than those in typical CIDP (p = 0.004 and p = 0.001) and DADS (p = 0.000 and 0.007) patients. Although the F-wave latency of tibial nerves was long in typical CIDP patients, a definite F-wave was absent in some patients, which was especially serious in typical CIDP patients, whose 19 (29.69%) median nerves, 28 (43.75%) ulnar nerves and 33 (51.56%) tibial nerves were absent. For DADS patients, 3 (25%) median nerves, 2 (16.67%) ulnar nerves and 4 (33.33%) tibial nerves were absent, while for LSS patients, the F-waves of all nerves could be drawn. There was a significant discrepancy in the frequency of F-wave absence among typical CIDP, DADS and LSS patients in the ulnar and tibial nerves (p = 0.006 and 0.003)  years; the additional 19 typical CIDP patients were converted from 2 DADS, 1 LSS, 8 pure motor and 8 pure sensory patients. Eight patients had a diagnosis of DADS at the time of onset, whose symptoms and signs presented symmetrically in the upper (1 case) or lower (7 cases) distal limbs; then, 2 (25%) of them progressed to typical CIDP 1 and 5 years later, and the other patients still had DADS after a duration of 2.5  years. Six patients were diagnosed with LSS at disease onset, but the diagnosis was changed to DADS in only 1 (16.67%) patient half a year later; the diagnosis was then changed to typical CIDP 1 year later, and the other 5 patients still had DADS after 3  years. Furthermore, 8 of 9 (88.89%) pure motor CIDP patients progressed to typical CIDP after 5.25  years, and all 8 (100%) pure sensory CIDP patients progressed to typical CIDP 0.96  years later. Figure 19. In this study, we applied the diagnostic criteria for EFNS/PNS and explored the comparison of clinical features, MRN, electrophysiology and progression for different CIDP subtypes, as very little research exists in the literature21. Our study showed that the values of CSF and ODSS in typical CIDP patients were higher than those in DADS and LSS patients. MRN and electrophysiology play important roles in the diagnosis of CIDP and in the differential diagnosis of CIDP and other peripheral neuropathies. Although CSA and CSF were different in CIDP patients with typical and atypical variants, disease severity  may be an important confounder that would need to be addressed in larger studies with multivariate analysis24. The results of this study indicated that the SCVs of the median and ulnar nerves in LSS patients were slower than those of typical CIDP and DADS patients, and the nerve root CSAs of the brachial and lumbosacral plexuses in typical CIDP patients were significantly thicker than those in DADS and LSS patients. To assess the progression of the disease, we retrospectively classified patients according to the symptoms at the time of disease onset and then recorded the rate of progression from atypical CIDP subtypes to typical CIDP at certain times. We found that fewer DADS and LSS patients progressed to typical CIDP patients than pure motor and sensory CIDP patients and that pure sensory CIDP patients progressed to typical CIDP faster than pure motor CIDP patients.CIDP is classified as typical and atypical CIDP variants according to different definitions20. The outcome of our study was that age, onset age, duration and were not different among typical CIDP, DADS and LSS patients, which was the same as the results of a recent report from Nagoya University, Japan25. These differences in several studies might be caused by the use of different phenotypic standards or the different geographical locations, but a similar result was that we all found that typical CIDP patients had more serious disability scores than DADS and LSS patients. Currently, only two Japanese studies have compared the electrophysiology results of typical and atypical CIDP, but these studies only analysed the median, ulnar and tibial nerves, whereas our data included the addition of the radial, peroneal and sural nerves and not only included motor conduction but also sensory conduction25. Our study revealed that the MCVs of the nerves showed no significant differences among the groups, and the CMAPs of almost all typical CIDP nerves were the lowest compared with those of the other groups, which was consistent with the previous series. Our findings also showed that the rate of absent F-waves in typical CIDP patients was highest; thus, the finding that the F-wave latency of the tibial nerve in DADS patients’ was longer than that in typical CIDP patients was not accurate, as shown in the data. In accordance with a previous report, the SCVs of typical CIDP nerves were slower than those of other nerves, which was contradictory to our finding that the SCVs of LSS nerves were the slowest25. In terms of the reason for this discrepancy, we consider the difference in patients’ essential characteristics to be important. As these studies all have small sample sizes and as the age, sex, and disease duration of patients all have significant differences, the results will have bias according to the different clinical features. To the best of our knowledge, no papers have compared the CSAs of nerve roots among CIDP subtypes. In our study, the CSAs of nerve roots in the typical CIDP group were significantly larger than those in the DADS and LSS groups, which indicated that inflammation and demyelination of proximal peripheral nerves were more serious in the typical CIDP group than in the other groups. To assess the progression of atypical CIDP, we retrospectively analysed the symptoms at the onset of disease and during the following years, and we found that 70.45% (31/44) of patients first had atypical CIDP and that 61.29% (19/31) of them had progressed to typical CIDP at the end of the follow-up, 3.33  years later, a result that was similar to a previous study8. The rates of DADS and LSS (25% and 16.67%) progression to typical CIDP were significantly lower than those of pure motor and pure sensory progression (88.89% and 100%) after a mean disease duration of 3.3 years. A similar finding exists between this study and a previous Italian study: we both found that the highest progression rate was for pure sensory CIDP and that DADS showed a lower rate of progression, while the difference between the studies was that the Italian study reported rates of 24% for DADS, 36% for LSS, 32% for pure motor and 48% for pure sensory in terms of the progression to typical CIDP in 5 years, and the percentage values at 10 years were 39%, 63%, 64%, and 77% 8. We believe that this difference may be caused by the following three reasons. First, we had different follow-up times and numbers of volunteers, and it is clear that the progression rate was associated with the disease duration. Second, the ethnical differences and genetic backgrounds between Italy and China may represent reasons for the different rates of disease progression. Finally, several studies have shown that different treatment initiation times and treatment regimens may also lead to different results28. The uneven distribution of medical resources and limited therapeutic levels in China lead to the late start of treatment for patients, and most patients are treated with hormones; only a few patients have received a single course of IVIg (intravenous immunoglobulin). It is possible that the unequal medical level caused our atypical CIDP patients to progress to typical CIDP faster and more frequently.It has been reported that patients with DADS have an older onset age than CIDP patients, and other subtypes were not significantly different when compared with typical CIDP in a large database study of Italian CIDP patients; these results were in contrast to the results of a Japanese study that included 139 CIDP patients in whom LSS patients were younger than typical CIDP patientsOur results showed that the disability scores and the CMAPs of nerves were lowest in typical CIDP patients and that the CSAs of nerve roots in this group were larger than those in the other groups, which indicated that typical CIDP was more severe than other subtypes not only in terms of clinical and electrophysiology factors but also in terms of MRN factors; this also suggested that peripheral nerve damage in the typical CIDP group was most serious not only in proximal nerve roots but also in distal nerves. One phenomenon that should be pointed out is that we defined patients as having pure motor or pure sensory CIDP according to their symptoms, while the electrophysiology results of 8 pure motor and 8 pure sensory patients who progressed to typical CIDP showed both sensory and motor involvement; however, the electrophysiology results of the 1 pure motor patient who did not progress to typical CIDP showed that only motor nerves were affected. It is worth considering whether the classified criteria for subtypes should be strict, such as defining them not only by the symptoms but also by the performance of electrophysiology.30. The low incidence of variant CIDP is an irreversible fact, and we are currently unable to collect more medical records. Second, we did not discuss the treatment responses for different subtypes. As a retrospective-prospective single-centre small-sample study, we retrospectively collected medical records and prospectively measured patients’ electrophysiology and MRN data. In terms of the treatment, our study did not provide any intervention, so it is not appropriate to evaluate the effects of various treatments. As far as we know, many large prospective studies have evaluated and discussed the advantages of these treatment effects31.There are several limitations in our study. First and foremost, the main limitations were that it was a study with a small sample size in the validation set, and bias was difficult to avoid. The incidence rate for CIDP is 0.33 per 100,000 person-years, and the 5 subtypes of atypical CIDP account for only 18% of all CIDP patients, which increases the difficulty of data collectionIn conclusion, despite the limitations of the study, our data indicated that typical CIDP was more severe than other subtypes not only in terms of clinical and electrophysiology factors but also in terms of MRN factors. Pure motor and pure sensory CIDP were more inclined to progress to typical CIDP than DADS and LSS, and the progression rate of pure sensory CIDP was faster than that of other subtypes. Finally, we suggest that classified criteria should include not only symptoms but also electrophysiology results.2. Of the 45 patients, 32 had typical CIDP, 6 had DADS, 5 had LSS, and 1 had pure motor CIDP at the beginning of our study. The number of pure motor and sensory CIDP patients was too low to analysis in the prospective part, so they were just be mentioned in the retrospective part. The ODSS was used as a disability score for the clinical assessment ranging from 0 (“no signs of disability”) to 12 (“most severe disability score”).Our study was a retrospective-prospective study of a consecutive series of 45 CIDP patients collected in the clinic and during hospitalization at Renmin Hospital of Wuhan University from January 2016 to May 2019. We used the electrodiagnostic criteria of EFNS/PNS for the diagnosis of CIDP, and we subclassified the patients into typical and atypical CIDP patients based on the clinical criteria in order to perform a retrospective analysis of the diagnosis at onset and of the progression throughout the course of diseaseWritten informed consent was obtained from all patients before participation. The Clinical Research Ethics Committee approved this prospective study at Renmin Hospital of Wuhan University (2017K-045), and all procedures were performed following the relevant guidelines/regulations in the Declaration of Helsinki.Conduction studies and F-wave evaluations of the median, ulnar, tibial, radial, peroneal, and sural nerves were performed with standard surface stimulation and recording techniques by a Keypoint4 electromyograph from Medtronic (Denmark). The patients were lying flat on the examination bed, and the skin temperatures were maintained above 32 °C in the limbs. The parameters measured included the motor nerve conduction velocity (MCV), compound motor action potential (CMAP), F-wave latency (F-Lat), sensory nerve conduction velocity (SCV), and sensory nerve action potential (SNAP). Electrophysiology was performed in patients by two professional doctors, and all procedures fulfilled the criteria of EFNS/PNS for CIDP.3, slice thickness = 1.0 mm, slice gap = 0 mm, and slice = 144. The acquisition time for imaging of the brachial and lumbosacral plexuses was 20 min.All participants were prospectively examined with a 3.0 T MR scanner  using three-dimensional sampling perfection with application-optimized contrast and different flip angle evolution (3D SPACE) sequences with a neck matrix coil, and three-body matrix anterior coils were applied. Subjects were placed in the gantry in the supine position with the head in the neutral position and instructed to breathe normally. The contrast agent  was intravenously administered before the brachial and lumbosacral plexuses were enhanced by scanning. The 3D SPACE parameters were as follows: TR/TE = 3000/270 ms, FOV = 448 × 448 mm2, voxel size = 1.0 × 1.0 × 1.0 mmMaximum intensity projection (MIP) images were reconstructed by built-in 3D postprocessing software . The bilateral cross-sectional area (CSA) of the nerves at the C7-C8 and L4-S1 levels was measured on the coronal plane. All work was completed independently by two senior radiologists blinded to all of the patients’ information, and the CSA (nr-CSA) of the nerve roots on each side of the brachial and lumbosacral plexuses was calculated separately.We compared the electrophysiology and MRN results of the nerve roots in the plexuses in typical and atypical CIDP patients and assessed the frequency of progression from atypical CIDP to typical CIDP.Statistical analysis was performed in SPSS 21.0 . Values conforming to a normal distribution are shown as the mean ± standard deviation (SD); otherwise, they are expressed as the medians and quartiles . Nonparametric tests  and Bonferroni correction were used for continuous variables, and chi-square tests were used for categorical variables. Two-sided P values were calculated for all analyses. P < 0.05 was considered significant.


Cochlear implant (CI) users have more difficulty understanding speech in temporally modulated noise than in steady-state (SS) noise. This is thought to be caused by the limited low-frequency information that CIs provide, as well as by the envelope coding in CIs that discards the temporal fine structure (TFS). Contralateral amplification with a hearing aid, referred to as bimodal hearing, can potentially provide CI users with TFS cues to complement the envelope cues provided by the CI signal. In this study, we investigated whether the use of a CI alone provides access to only envelope cues and whether acoustic amplification can provide additional access to TFS cues. To this end, we evaluated speech recognition in bimodal listeners, using SS noise and two amplitude-modulated noise types, namely babble noise and amplitude-modulated steady-state (AMSS) noise. We hypothesized that speech recognition in noise depends on the envelope of the noise, but not on its TFS when listening with a CI. Secondly, we hypothesized that the amount of benefit gained by the addition of a contralateral hearing aid depends on both the envelope and TFS of the noise. The two amplitude-modulated noise types decreased speech recognition more effectively than SS noise. Against expectations, however, we found that babble noise decreased speech recognition more effectively than AMSS noise in the CI-only condition. Therefore, we rejected our hypothesis that TFS is not available to CI users. In line with expectations, we found that the bimodal benefit was highest in babble noise. However, there was no significant difference between the bimodal benefit obtained in SS and AMSS noise. Our results suggest that a CI alone can provide TFS cues and that bimodal benefits in noise depend on TFS, but not on the envelope of the noise. Cochlear implants (CIs) are auditory prostheses offered to individuals who are severe-to-profoundly deaf. CIs can partly restore hearing by electrically stimulating auditory-nerve cells directly, thereby bypassing the degenerated hair cells in the cochlea. The performance of CIs has greatly improved since their inception by the advent of ongoing technological advances in stimulation strategies, processing power, and front-end processing. However, speech understanding of CI users in noisy environments remains a particularly challenging task. In fact, CI users are more susceptible to noise than normal-hearing listeners , periodicity (50–500 Hz), and fine structure information   feature. After envelope extraction, SpecRes identifies the dominant spectral peak of each of the frequency bands. These spectral peaks are used to modulate the pulse rate of the carrier at the corresponding frequency to introduce TFS in the electric speech signal. Reportedly, HiRes 120 strategies are capable of representing TFS up to frequencies of approximately 2300 Hz  that complements the conventional CIS strategy with TFS by introducing variable pulse rates on the apical electrodes. However, like SpecRes, the results obtained with FSP and related fine structure strategies have been mixed: while some studies found significant improvements of speech understanding in noise  in the contralateral ear , their overall spectrum resembled the female voice of the target speech , non-randomized (subjects were selected from the database of the institute according to the criteria listed below), and non-controlled (we used a cross-over design where subjects were their own control). Fifteen unilaterally implanted subjects  with an Advanced Bionics system were included in this study. The demographics are listed in Table All subjects had been fitted with a contralateral HA  before testing and had been using it at home for at least 4 weeks. They used a bimodal fitting rule that emphasizes audibility of low-frequency sounds which carry TFS important for speech understanding in noise  levels and maximal comfortable (M) levels. The frequency range of the acoustic band-pass filter was set at “standard,” instead of “extended low,” which is currently the default setting. The “standard” filter option deploys a low-pass cutoff of 350 Hz (on electrode 1) and a high-pass cutoff of 8700 Hz (on electrode 16). The Naída Link HA was also fitted using the subject’s own, home-use settings. The primary outcome measure was the speech reception threshold (SRT), i.e., the signal-to-noise ratio (SNR) where a 50 % correct word score was obtained. To measure speech recognition, the Dutch/Flemish Matrix test  was tested. The first 4 sessions were used to measure SRTs in SS and babble noise. Noise type was alternated between sessions. The initial noise type was randomized. Hence, after 4 sessions, a test and a re-test were obtained for both noise types. In one subject, the re-test of the babble noise could not be performed, because the subject left the study for health reasons unrelated to hearing. AMSS was tested and re-tested in 11 subjects in a fifth session. In the remaining 3 subjects, these measurements could not be performed due to time constraints. Per session, at least 12 speech recognition tests were administered, each run lasting approximately 5 min. More tests were sometimes needed when tests were considered unreliable, e.g., when the SRT was not stable at the end of the run. During the first 4 sessions, additional data on noise reduction algorithms  were obtained that are not presented here. The present data were obtained using omnidirectional microphone settings for CI and HA, and no beamforming or binaural processing was applied in the CI or HA. No other speech enhancement algorithms  were used. Only the processor microphone of the CI was used .In each session, listening condition  was randomized. In the CI-only condition, the contralateral ear was not occluded. During the start of each session, the experience of the subject with the HA was informally assessed. We enquired whether they used the HA, how many hours per day they wore it, and what the advantages and disadvantages of the HA were, and we asked them to give the HA a single overall rating in terms of their overall satisfaction and experience with the HA as a complement to their CI, ranging from 0 (“it is a terrible experience”) to 10 (“the HA is a perfect add-on to my CI”). The daily overall use was confirmed through data logging from the HA.The first two runs of a session were reserved for practice runs to minimize training effects during the session. During these practice runs, the subjects were encouraged to use a sheet with the 50 words included in the Dutch matrix test. For the first few subjects, the practice runs were both performed in the presence of noise. We noticed, however, that the subjects benefited more from doing the first run in quiet  and the second one in the presence of noise. The resulting SRT of the second trial minus 4 dB was used as the starting SNR in subsequent runs. During practice, subjects were listening bimodally.Three noise types were used, namely steady-state (SS), babble, and amplitude-modulated steady-state (AMSS) noise. Sample waveforms can be found in Fig. The SS noise is included in the speech material of the Dutch/Flemish matrix test  noise. It was generated by extracting the envelope from the babble noise by determining the magnitude of its analytic signal Marple . The resl × w × h). Noise was delivered through 8 surround loudspeakers  distributed symmetrically around the listener in 3D space . The frequency characteristic of the surround loudspeakers was characterized similarly by generating uncorrelated SS noise through all of them and recording the frequency spectrum in the middle of the noise field Fig. . The reaCalibration was performed using a sound level meter  with the microphone positioned in the middle of the room at the position where normally the subject’s head would be. The SS noise was calibrated at 60 dBA by playing it over the 8 surround loudspeakers. The speech material was calibrated by playing the loudness-matched, speech-weighted SS noise over the center loudspeaker in front of the listener. The babble noise and AMSS noise were corrected for the overall sound level digitally by matching the root-mean-square value of the complete file length to that of the SS noise. Because there were 8 uncorrelated noise sources, the depth of amplitude modulation in the 8-talker babble and 8-“talker” AMSS in the diffuse noise setup was substantially reduced Fig. . Howeverprior). HAprior was introduced, because 6 subjects included in this study had been using their HA for only 4 weeks after being recruited for this study. Four co-variates were accounted for in the model, namely two measures of residual hearing (PTA125–500 and PTA500–2000), performance with HA alone (SRTHA), and age. Better residual hearing may be correlated with higher bimodal benefit   to calculate PTA500–2000. The more frequently used PTA500–4000 was not used, because in 6 out of 15 subjects the threshold at 4000 Hz exceeded the maximum output level of the audiometer. Age was taken into account as it may impact a multitude of variables, ranging from speech understanding in noise to attention span and listening fatigue during testing  using SPSS 23 for Windows . Two dependent variables were tested separately, namely SRTs and bimodal benefits. Bimodal benefits were calculated by subtracting the SRT obtained in the CI-only condition from the SRT obtained when listening bimodally. SRTs were used to investigate the effect of the three noise types on SRTs, i.e., to test whether amplitude-modulated noise decreases speech recognition more than SS noise. Bimodal benefits were used to investigate whether the benefit of bimodal hearing depended on noise type. Several fixed factors were included in the LMM, namely (1) noise type (N) to test the effects of TFS; (2) listening modality (CI + HA) to investigate the effect of bimodal hearing; and (3) prior HA use (HAting Lee . SubjectN = 15), HA only , and bimodal hearing (N = 15) is shown in Fig. P < 10−6). Bimodal hearing improved the overall SRT by 1.3 dB (P < 0.0082). None of the other factors included in the LMM significantly affected SRTs. An overview of the model with its parameter estimates is shown in Table SRTs were obtained to compare speech recognition in the presence of SS and babble noise. An overview of the SRTs obtained with CI only  is 1 for babble noise or 0 for SS noise; SRTHA is the SRT when listening with a HA alone; PTA125–500 is the mean pure-tone audiogram across 125, 250, and 500 Hz; and age is the subject’s age. Suppose a bimodal listening subject of 65 years who was already using a HA when recruited in the study. This person had a PTA125–500 of 70 dB, was tested in babble noise, and had an SRT of + 15 dB with a HA alone. The predicted SRT then becomes: − 21 − 1.3 + 6.5 + 0.7 + (0.2 · 15) + (0.1 · 70) + (0.1·65) = + 1.4 dB. Removing the HA will yield a predicted SRT that is less favorable, namely + 2.7 dB.P = 0.036). None of the other factors in the model had a significant effect on the bimodal benefit  were entered as the dependent variable Fig. . This seit Table . ParametB is the bimodal benefit  and + 4.1 dB is the intercept. The remaining parameter symbols are equal to those in Eq. mentclass2pt{minimt = 17, P < 10−6). AMSS also resulted in higher SRTs than SS noise , but less pronounced than the babble noise (P < 10−6). The bimodal benefits were examined including the subpopulation where AMSS was tested using the same parameters as in Eq. P = 0.97), whereas in babble noise the benefit was significantly greater than in SS noise . From the 5 additional parameters entered in the four LMMs, namely PTA125–500, prior HA use, SRT with HA only, and age, none had a significant effect on the SRT or bimodal benefit  between the two parameters that was not significant  = 0.84, P = 0.38).Because we did not occlude the contralateral ear, the difference in SRTs between babble and AMSS noise in the CI-only condition might have been caused by the contralateral ear providing TFS cues. To examine this, the difference SRTs were plotted against PTA500 Fig. . The difTo gain insight into the cause of the differences between the SRTs in the babble noise and AMSS, we visualized the TFS in the pulse-train output of the CI in the two noise types by running a simulation of the Advanced Bionics HiRes 120 speech processor kindly provided by Chen Chen . The simulator accepted any audio wave file and processed it the same way as the speech processor would do  always wore their HA at home (in combination with their CI). Two subjects (13 %) wore it for only a few hours per day. One of these two was the only person in the study population who preferred not to wear the HA. This person reported that the HA added nothing to the electric hearing but noise. This was not caused by little residual hearing, as the pure-tone thresholds were 25, 50, and 75 dB at 250, 500, and 500 Hz, respectively, all well within the study inclusion criterion. Contrary to this person’s subjective report, the SRTs actually improved by 0.2 dB and 0.8 dB in SS and babble noise, respectively. The one person who subjectively indicated to have worse speech understanding in noise with the bimodal fitting actually improved in both SS and babble noise by 2 dB and 5 dB, respectively. Fourteen out of 15 subjects (93 %) reported at least one benefit of the device, including improved sound quality, better speech understanding, and directional hearing during everyday use. 9 out of 15 reported disadvantages (60 %), including an increased hindrance caused by background noise, a negative impact on speech understanding in general, and outer ear discomfort due to the ear mold. The median rating, on a scale of 0 (HA is useless) to 10 (it is a perfect add-on to the CI) was 8.0. In Table  % alwaysF0 information, which in turn aids in segregating speech from background noise  cues that are lacking in a CI  had significant effects on the SRT or bimodal benefit (Tables 125–500 lends circumstantial support for the notion that wearing a contralateral hearing aid can be beneficial, even when the degree of hearing loss in the non-implanted ear is severe or profound (Ching et al. Apart from bimodal hearing and noise type, none of the other factors (PTAt Tables  The lackOur results support the notion that amplitude-modulated noise is particularly detrimental to speech recognition by CI users. In addition to temporal modulation, the TFS of the babble noise likely also affected speech recognition in the CI-only condition, which was an unexpected result, as it is generally assumed that TFS is not available after CIS-based speech coding. The current study also suggests that the benefit of bimodal hearing for speech recognition was greater in babble noise than in SS noise. This difference in benefit may have been dependent on the TFS cues present in the babble noise that were conveyed by the HA, and not on the amplitude-modulated character of the babble noise.


Gastrointestinal (GI) mucormycosis is a rare and often deadly form of mucormycosis. Delayed diagnosis can lead to an increased risk of death. Here, we report a case of GI mucormycosis following streptococcal toxic shock syndrome in a virologically suppressed HIV-infected patient.Rhizopus microsporus strains in GenBank (GenBank accession numbers KU729104 and AY803934). As a result, she was treated with liposomal amphotericin B. However and in spite of receiving appropriate treatment, our patient developed recurrent massive upper GI bleeding from Dieulafoy’s lesion and succumbed to her disease on day 33 of her admission.A 25-year-old Thai woman with a well-controlled HIV infection and Grave’s disease was admitted to a private hospital with a high-grade fever, vomiting, abdominal pain, and multiple episodes of mucous diarrhea for 3 days. On day 3 of that admission, the patient developed multiorgan failure and multiple hemorrhagic blebs were observed on all extremities. A diagnosis of streptococcal toxic shock was made before referral to Siriraj Hospital – Thailand’s largest national tertiary referral center. On day 10 of her admission at our center, she developed feeding intolerance and bloody diarrhea due to bowel ischemia and perforation. Bowel resection was performed, and histopathologic analysis of the resected bowel revealed acute suppurative transmural necrosis and vascular invasion with numerous broad irregular branching non-septate hyphae, both of which are consistent with GI mucormycosis. Peritoneal fluid fungal culture grew a grayish cottony colony of large non-septate hyphae and spherical sporangia containing ovoidal sporangiospores. A complete ITS1–5.8S-ITS2 region DNA sequence analysis revealed 100% homology with Diagnosis of gastrointestinal mucormycosis can be delayed due to a lack of well-established predisposing factors and non-specific presenting symptoms. Further studies in risk factors for abdominal mucormycosis are needed. Mucorales (Mucoromycotina) [Mucormycosis is a rare and very serious opportunistic infection that is caused by fungi belonging to the order ycotina) , and it ycotina) . This diycotina) . Six cliRhizopus microspores that developed shortly after the diagnosis of Streptococcus pyogenes toxic shock syndrome in a virologically suppressed HIV-infected patient. According to our review of the literature, this is only the second case of gastrointestinal mucormycosis following S. pyogenes toxic shock syndrome to be reported.Increased morbidity and mortality is often caused by a delay in diagnosis and treatment since most patients present with non-specific gastrointestinal (GI) symptoms, and definite diagnosis can only be made by biopsy of the suspected area during surgery or endoscopy. Culturing gastric aspirates can also be used as an alternative method for diagnosis of GI mucormycosis, but its specificity is low due to possible contamination , 3. HereA 25-year-old Thai woman with HIV infection and Grave’s disease was referred to Siriraj Hospital  in February 2017 due to symptoms that included high-grade fever, vomiting, abdominal pain, and multiple episodes of mucousy diarrhea for 3 days. Our hospital is Thailand’s largest university-based national tertiary referral center.+ count of 419 cells/mm3, and a CD4+ percentage of 31% at 5 months prior to this admission. Her Grave’s disease was diagnosed in 2005, it was successfully treated with radioactive iodine therapy, and it was maintained with oral thyroxine.She was diagnosed with HIV infection in 2004, and she maintained a virologically suppressed status via the use of tenofovir, emtricitabine, atazanavir, and boosted ritonavir with an absolute CD4Streptococcus pyogenes was isolated from blood cultures. In contrast, conventional stool culture reported no growth.This patient was initially admitted to a private hospital where she presented with a hypotensive blood pressure of 65/27 mmHg and severe metabolic acidosis. She was diagnosed with severe gastroenteritis and septic shock, and she was empirically treated with ceftriaxone and metronidazole. However, during that admission, she developed multiorgan failure, including acute respiratory distress syndrome, acute kidney injury, and profound hypotension, even after receiving a high dose of both vasopressor and hydrocortisone. She was then intubated and antibiotic therapy was changed to meropenem. Before referral to our center on day 3 of her private hospital admission, multiple hemorrhagic blebs were observed on all extremities, and S. pyogenes toxic shock syndrome and multiorgan failure, she received supportive care with continuous renal replacement therapy. On day 5, her condition improved and vasopressor was discontinued. Antibiotic therapy was de-escalated from meropenem to penicillin and clindamycin. However, she still had persistent fever, bloody diarrhea, and hemorrhagic blebs at both hands. Necrotizing fasciitis at the left hand was suspected, but the patient and family refused amputation.Upon her arrival at Siriraj Hospital with a diagnosis of On day 10, she developed feeding intolerance with continued bloody diarrhea, distended abdomen with ascites, hypoactive bowel sounds, and high-grade fever with septic shock. The abdominal fluid analysis was consistent with secondary bacterial peritonitis. Abdominal computed tomography (CT) , carbapenem-resistant K. pneumoniae (CRE), and unspecified yeast species, her antimicrobial therapy was changed to piperacillin/tazobactam and fosfomycin, linezolid, colistin, and fluconazole.Since initial ascitic fluid culture grew pan-drug resistant Mucorales fungi. Moreover, peritoneal fluid fungal cultures grew a grayish cottony colony on Sabouraud dextrose agar following 3 days of incubation at 25 °C, and demonstrated large non-septate hyphae and spherical sporangia containing ovoidal sporangiospores. To exclude other possible co-infection causing bowel necrosis, immunohistochemical stain for cytomegalovirus and an acid-fast stain for Mycobacterium were additionally performed on the bowel tissue biopsies, and all tests showed negative results. A complete ITS1–5.8S-ITS2 region DNA sequence analysis of the fungus showed 100% homology with Rhizopus microsporus strains in GenBank, including standard strains ATCC 22959 and ATCC 200758 (GenBank accession numbers KU729104 and AY803934). However, a variety level could not be determined due to a limitation of the ITS method [Histopathology of the small bowel Figs.  and 3 reRhizopus microsporus by fungal culture and ITS sequence analysis. The patient was then treated as GI mucormycosis with liposomal amphotericin B at a dosage of 300 mg per day (5 mg/kg/day). After 12 days of amphotericin B treatment (day 33 of her admission), she developed recurrent massive upper GI bleeding from Dieulafoy’s lesion and she succumbed to her disease.Finally, the definite diagnosis of GI mucormycosis was made based on the evidence of intestinal tissue invasion by a non-septate fungus, which was later identified as Gastrointestinal (GI) mucormycosis is a rare disease with an extremely high mortality rate. It most commonly involves the stomach, followed by the colon and the small bowel , and traStreptococcus pyogenes bacteremia. Her abdominal symptom then worsened leading to a diagnosis of GI mucormycosis, which occurred 10 days after her diagnosis of streptococcal toxic shock syndrome. Similar to the first case report [Rhizopus microsporus. Therefore, streptococcal toxic shock syndrome might be considered a newly discovered predisposing factor for this extremely rare form of mucormycosis. Increased risk of mucormycosis in this setting may be due to two possible mechanisms. First, since S. pyogenes produces a wide variety of exotoxins with superantigen activity [S. pyogenes toxic shock syndrome adversely affects normal gut flora, especially anaerobic bacteria, and this can lead to significant overgrowth of pathogenic fungal organisms [To our knowledge, this is only the second case of gastrointestinal mucormycosis after streptococcal toxic shock syndrome to be reported , and thie report , there wactivity , these c+count of 419 cells/μL was not diminished to a level that rendered her susceptible to opportunistic pathogens (< 200 cells/μL). In fact, among 297 patients with invasive fungal infection in a large retrospective study of 1630 autopsies of patients with acquired immunodeficiency syndrome (AIDS) during 1984 to 2002 [+ count  and one or more predisposing factors [Interestingly, our patient developed GI mucormycosis without any well-established predisposing factor. Her absolute CD4 to 2002 , only tw factors .Mucorales DNA detection is a new and promising diagnostic tool, it is not yet widely used in routine diagnostic testing [Early diagnosis and treatment are crucial to prevent complications and death. However, early diagnosis is difficult due to non-specific sign(s) and symptom(s), and the lack of a diagnostic tool to confirm the disease. Although circulating  testing . In the Mucorales in vitro [The mainstay of treatment for mucormycosis is the surgical debridement of necrotic tissue to prevent the progression of the infection to vital structures or dissemination to other sites. Reduced blood supply to tissue due to vessel thrombosis means that adequate surgical debridement of these compromised tissues can enhance the penetration of antifungal agents into still viable infected tissue. Additionally, antifungal therapy should be initiated when mucormycosis is highly suspected , 15. Polin vitro . Posaconin vitro . Howeverin vitro . Combinain vitro . DespiteIn conclusion, GI mucormycosis remains a diagnostic and therapeutic challenge. Nonspecific complaints and the lack of well-established predisposing factors in our patient delayed the diagnosis of GI mucormycosis, and this resulted in worse outcome and death – even after appropriate treatment was given. Studies in risk factors for abdominal mucormycosis are needed.


Aedes albopictus contribute to the dispersion of the dengue viruses. Frequent and injudicious use of synthetic insecticides led to the evolution of resistant phenotypes in Ae. albopictus which necessitates the search for an alternative of current control strategies. Developing a long-lasting and environmentally safe tactic based on knowledge of ecology and population dynamics of Ae. albopictus is critical. Therefore, with a view towards biological control and ecology, the effect of entomopathogenic fungi (EPF) Beauveria bassiana on filial and first filial generations of Ae. albopictus were studied. Investigations showed 87.5% adulticidal activity leading to altered fecundity and adult longevity in a filial generation. The lethal (LC50) and sublethal (LC20) concentrations of B. bassiana were applied to filial generation (F0) to study demographic parameters in the first filial generation (F1). Results showed reduced net reproductive rates (o)R intrinsic rate of increase (r), and mean generation time (T) compared to uninfected controls. Prolonged larval and pupal duration were observed followed by reduced longevity of male and female adults. Fecundity in the first filial generation was significantly changed with the lethal and sublethal concentrations of B. bassiana. Thus, it is concluded that B. bassiana has the potential to play a vital role in integrated mosquito management strategies.Dengue fever is one of the most rapidly spreading arthropod-borne diseases. Diurnal vectorial properties of  Aedes albopictus, more than 100 nations in tropical and subtropical regions around the world are confronting the dangers of dengue fever, yellow fever, and chikungunya [Ae. albopictus makes it more dangerous than other mosquito species, it also facilitate the rapid transmission of diseases [Mosquito-borne diseases have been a primary concern for the human population for a long time. Due to diseases . Moreovediseases , environdiseases ,5. Non-tdiseases ,7,8 and diseases ,10,11. Adiseases ,19,20,21diseases ,23,24.Ae. albopictus are better known. Population dynamics and population ecology of insects play a vital role in the development of long-lasting control with EPF [Ae. albopictus can help to determine the best time and stage upon which EPF should be applied for management [EPF can be used more efficiently if the impacts of the life cycle of with EPF ,25,26. Lnagement ,28.Ae. albopictus have been conducted with a focus on immature stages but the adult populations  are overlooked [Life table studies for erlooked . Life taerlooked ,31,32. Terlooked  subsequeerlooked , can difAe. albopictus, and assessments of Beauveria bassiana isolated from two different sources were done. The best isolate was used to examine transgenerational effects on demographic parameters of filial offspring and first generations offspring by utilizing the age stage two-sex life table, which will guide us towards the effective use of B. bassiana at the most impactful time and stage of Ae. albopictus. This will contribute to development of a useful, and eco-friendly tool for integrated pest management of this urban pest.The current study was planned with Ae. albopictus (Foshan strain) eggs were collected from Guangdong Center for Disease Control and Prevention Guangzhou, China (2017). Eggs were brought on disinfected media  to the Laboratory of Bio-Pesticide Innovation and Application of Guangdong Province, College of Agriculture, South China Agricultural University, Guangzhou, China. Filter papers containing the eggs were placed in glass beakers (200 mL) containing water for hatching under controlled  laboratory conditions (pathogen-free environment) [ronment) . Two-dayronment) . Pupae wronment) . Male anB. bassiana (Bb-01 and Bb-10), were obtained from the Laboratory of Insect Microbiology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan [Two soil extracted isolates of Pakistan ,37. Bb-0Isolates were passaged multiple times to prevent aging . A two-wB. bassiana (Bb-01 and Bb-10) were screened out against the adult  of Ae. albopictus. Five concentration  were prepared for both isolates, whereas 0.05% Tween-80 (Sigma-P1754) diluted in distilled water was taken as tween control and distilled water was a general control [Two isolates of  control . Plastic control ,13,22. A50 was calculated for both isolates of B. bassiana (POLO-PC software). The fungal isolate with the lowest LC50 was chosen for further experimentation with the age stage two-sex life table.The LCB. bassiana was again tested on blood-fed and non-blood-fed females, five concentrations  were prepared and applied with the same methodology as described above. Females used in experimentation were 2 days old (24 h starved) and concentrations were applied 8 h post blood-feeding.A selected isolate of 50, LC20) for the life table studies were practically evaluated against adults of Ae. albopictus. For experimentation jars (10 adult/replication) sprayed with desired concentrations were used with the same procedure as described above.Lethal and sublethal concentrations (LC50) and sublethal (LC20) concentrations separately, in treated jar assays  water diluted 0.05% Tween-80 (Sigma-P1754) was used as control. Mortality was observed every 24 h for 7 days, after the seven days of treatment the remaining adults of filial generation (F0) were copulated (1pair/cage) in plastic cages covered with a white cloth. Blood meals were provided every four days until the death of females . Glass beakers with wet filter paper were used as ovipositional sites. Fecundity and longevity were observed until the death of every individual of the filial generation [A total of 1000 newly emerged adults (1:1) were selected for bioassays. Males and females (250 each) were separated with an electric aspirator and subjected to Lethal . Eggs were placed individually on disinfected plastic trays (150 mL distilled water) without fungal exposure in pathogen-free environment. Powered fish food  was individually given to larvae as food. The transgenerational effects were studied from larva to adult stage. Data were recorded every 12 h until the death of all individuals. On the emergence of adults, individuals of the first filial generation were paired and shifted in cages for seeking the data regarding longevity and fecundity.Eggs laid by filial generations, 100 eggs were collected from each group  was used for the calculation of standard errors for life table parameters [http://140.120.197.173/Ecology/prod02.html) (Chung Hsing University).The calculation of lethal and sublethal concentrations was conducted by using POLO-PC software . Mortalirameters . The prorameters ,46 (httpR0), which shows a total number of offspring by an individual throughout its life was calculated via the equationxl, the probability of a newly laid egg surviving to age x can be calculated asxm is mean fecundity of individuals at age x can be obtained from the following equationIn age stage two-sex life table net reproductive rate (The intrinsic rate of increase (r) was evaluated utilizing the iterative bisection strategy and adjusted with the Euler–Lotka condition with the age-indexed (Goodman 1982).The finite rate was calculated asR0-fold of its population size at the stable age-stage distribution is called as mean generational time, and is calculated asxje, the length of time that an individual of age x and stage j is expected to live could be obtained from the equation below [xjv) was calculated according to [Length of time that a population needs to increase to on below (7)exj=∑rding to ,49 and wB. bassiana  revealed a direct relationship between concentration and mortality  dead specimens were put in humid chamber for conidal growth  and sublethal (LC20) doses for both isolates  of B. bassiana were calculated from pre-experimentation data  by contact assay in the jar. Non-significant results were seen (B. bassiana (Bb-01).Blood-fed and non-blood fed females of ere seen  between 50) and sublethal (LC20) concentrations of B. bassiana (Bb-01) were experimentally validated, lethal concentration LC50 showed 51.54 ± 0.98% adult mortality followed by sub-lethal concentration LC20 (23.11 ± 1.11).Calculated lethal (LC50) and sublethal (LC20) concentrations of B. bassiana (Bb-01), the effect of longevity and fecundity of Ae. albopictus  were seen . Female longevity also showed a similar tread to male longevity (days), where LC50 of Bb-01 presented the lowest longevity (22.22 ± 1.21) followed by LC20 of Bb-01 (27.65 ± 1.77) as compared to the control (30.07 ± 0.41). A significant reduction in fecundity  was also observed. Exposure to LC50 of Bb-01 results in the fewest number of eggs (189.31 ± 8.11) followed by the LC20 exposure (230.47 ± 9.32) and controls (357.33 ± 9.30).After the treatment of Lethal  concentration of B. bassiana, while 95% of egg hatching was observed after treatment of lethal (LC50) concentration of Bb-01. An opposite trend was observed in egg duration, where control (2.00 ± 0.01 days) and sublethal concentration (LC20) of B. bassiana (2.00 ± 0.01) showed prolongs the egg hatching duration, while early egg hatching (days) was seen in lethal (LC50) concentration (1.95 ± 0.54) of B. bassiana. Significantly different total larval duration was reported, LC50 of B. bassiana showed maximum (8.38 ± 0.16) development time (days) follow by LC20 (7.97 ± 0.01), while minimum developmental time (7.89 ± 0.03) was seen in the control group. In pupal duration (days), LC50 of B. bassiana showed minimum pupal duration (2.55 ± 0.59) then LC20 (3.00 ± 0.59) and control (3.00 ± 0.11). A significant reduction was seen in the life span of male Ae. albopictus, an increase in the concentration of B. bassiana had an inverse effect on the reduction of the male life span. Male adults of Ae. albopictus showed minimum life span (27 days) on LC50 of B. bassiana then LC20 (30.10 days) and control (30.00 days). A similar trend was observed in the female life span. Fecundity had an inverse relation with lethal and sublethal concentrations of Bb-01, females treated with LC50 of B. bassiana laid a minimum mean number of eggs , while females from LC20 of B. bassiana laid more eggs  then LC50. The maximum mean number of eggs was observed in control .For evaluation of transgenerational changes in the first filial generation of r) was inversely related to concentration, which varied from 0.27 to 0.25 and 0.23 in the control, LC20, and LC50 respectively. Mean finite rate of increase (λ) had a significant difference (per day) between control (1.32 ± 0.01), LC20 (1.29 ± 0.02) and LC50 (1.26 ± 0.06). The net reproduction rate (0R)  was high in control (133.0 ± 16.21) and then gradually decrease significantly in LC20 (89.16 ± 9.31) and LC50 (50.62 ± 8.31). Significant differences were also observed between mean generation times (T), 17.83 days for control and 17.80 and 17.09 days in LC20 and LC50 respectively (p < 0.05).Population parameters calculated with the help of the age stage two-sex life table are shown in Sxj) signifies that in the first filial generation overall life span of Ae. albopictus in the control group was longer and was reduced after treatment of LC20 and LC50 of B. bassiana (Exj) where treated group individuals had a lower life expectancy and overall life span  shows the maximum reproductive value of a stage in life span, adult females from the control group showed the highest peak of reproductive value as compared to lethal and sublethal concentrations of B. bassiana (p < 0.05). Egg-laying started 2 days post blood meal; in the beginning, controlled females showed a maximum number of eggs followed by females of LC20 and LC50. With time reduction in a mean number of eggs was seen in treated females.Age stage reproductive value  were screened against Ae. albopictus with both isolates showing noteworthy adulticidal activity. The isolate extracted from soil of (Bb-01) in Pakistan showed more virulence than the isolate from the soil of cold area (Bb-10) soil. Bb-01 provided 87.5% adult mortality which also goes in favor of previous studies where Ae. albopictus and Culex spp. showed 80–90% adult mortality after treatment of EPF [50 and high adulticidal activity, Bb-01 was selected for further studies to assess its transgenerational effects on the filial and first filial generation of Ae. albopictus.The life table of tracheal arthropods (insects) is directly related to the control of insects. Increased knowledge of insect stages, survival, and reproduction, can lead us towards promising and long-lasting control of insect pests ,53,54,55t of EPF ,40,56,57B. bassiana produces secondary products like beauvericin, bassianin, bassianolide, beauverolides, beauveriolides, tenellin, oosporein, and oxalic acid which evade the humoral and immune system of the insect [B. bassiana absorbs the sugar contents from the hemolymph of insect which contributes towards insect weakness and disrupts various biological parameters of insect pests [50) from Bb-01 which goes in favor of previous studies in Aedes spp and S. litura (Fabricius 1775) where EPF causes a reduction in egg hatching [Insect chitin made cuticle is the main line of defense against EPF. In the case of medical insects like mosquito, complete control  via EPF is not so easy. While EPF causes mortality in two weeks, an essential aspect is the effect of EPF on life parameters of mosquito. e insect ,59. Hyphct pests ,61. The hatching ,63,64.Musca domestica (Linnaeus 1758) and Culex spp. [EPF penetrates the cuticle and affects the fat body of the insect depleting energy resource which directly affects the insect stadium ,66,67, wlex spp. ,23,68.Ae. albopictus, adult control is the most important thing [Ae. albopictus adults will help in the control of vector-borne diseases [Ae. albopictus and Ae. aegypti had also shown a significantly short life span after infection of EPF [Anopheles spp. also showed low adult survival after the treatment of EPF [Rhynchophorus ferrugineus (Olivier) and Trogoderma granarium, where 20-30% reduced longevity was observed after treatment of EPF [In epidemiological models for diseases of nt thing ,70,71. Sdiseases . Our finn of EPF ,41,69. At of EPF ,74,75,76t of EPF ,78.Ae. albopictus. In past studies reduction in blood-feeding [Musca domestica and S. litura showed less mean number of eggs after the treatment of EPF [B. bassiana showed a significant effect on all demographic parameters of Ae. albopictus in a filial and first filial generation.The infection of EPF fluctuates the body temperature of females, resulting in the loss of appetite, which led to reduced fecundity . In curr-feeding , retarda-feeding . Musca dt of EPF ,68. B. bAe. albopictus population dynamics under the influence of B. bassiana. From our investigation, the conclusion can be drawn that B. bassiana has lasting effects on the developmental parameters of Ae. albopictus. Mainly the impact of the Bb-01 on adult longevity and female fecundity was significantly affected. Considering the impact of B. bassiana on transgenerational parameters of filial and first filial generation, it can be integrated with effective dengue vector control strategies.This study is first of his kind and provides basic yet important time-specific and age-specific information for a better understanding of