Between- and within-group analyses investigated treatment-related effects and their stability at a 70-day follow-up. Results: Overall, distress symptom severity was mild. Unlike the DIG, the IIG showed significant improvements in tinnitus-related distress. Some psychological epiphenomena, notably anxiety, slightly improved in both groups. Within-group analyses demonstrated the stability of the tinnitus-distress-related effects, alongside uncontrolled improvements of perceived stress and mood-related symptoms at follow-up. Conclusions: The investigated hearing therapy lastingly improves tinnitus-related distress in mildly distressed patients with chronic tinnitus and mild-to-moderate hearing loss. Beneficial psychological knock-on effects deserve further investigation.Background: The psychological effects of hearing aids and auditory training are underinvestigated. Objective: To assess the short- and long-term effects of an industry-developed auditory training on tinnitus-related distress, perceived stress, and psychological epiphenomena in patients with chronic tinnitus and mild-to-moderate hearing loss. Method: One-hundred-seventy-seven gender-stratified patients were randomized to an immediate [IIG] or delayed [DIG] intervention group. Following binaural hearing aid fitting, participants completed a CD-enhanced 14-days self-study program. Applying a randomized-controlled cross-over design, psychological measures were obtained at four times: pre-treatment/wait [IIG: t Chronic tinnitus denotes the longstanding >3 months) perception of sound without external acoustic stimulation . Tinnitu months pWhilst chronic tinnitus likely develops at the interface of various psychobiological influences , hearingPsychologically, chronic tinnitus, hearing loss, and difficulties with speech-comprehension-in-noise hold the potential to negatively affect individuals’ well-being—notably by causing or exacerbating anxiety, low mood, or perceived stress ,26,27,28Compared to a waiting, delayed-intervention group (DIG), an immediate intervention group (IIG) shows higher reductions in tinnitus-related distress and psychological distress following Terzo©  hearing therapy;Given the primarily audiological–cognitive focus of the intervention, treatment-related change may be most strongly reflected in TFI (vs. TQ or THI) scores;Any observed effects will be stable at a 70-day follow-up.The present study aims to fill this gap and applies a randomized, controlled, three-timepoint cross-over design to investigate the effects of an industry-developed hearing therapy  on tinnitus-related distress, perceived stress, and psychological epiphenomena in patients with chronic tinnitus and mild-to-moderate hearing loss. We hypothesized:Mage = 59.61, SD = 7.46) were recruited from Charité Universitätsmedizin, Berlin. Adults (aged ≥ 18 years) with a tinnitus duration of more than 3 months and mild-to-moderate hearing loss were included in the study  points on the Tinnitus Questionnaire with an assumed alpha of 0.05 and a power of 0.80, n = 58 subjects were required per arm. Assuming an average drop-out rate of 20% , seventy subjects were necessary. In the present study, the target n was eventually set to 75 treatment completers per arm.Between 2018 and 2020, 177 participants . Past pSee https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015312, accessed on 9 August 2021).Participants were informed about the scope and aims of the study and signed an informed consent agreement. The Charité Universitätsmedizin’s ethics committee approved the study (EA1/114/17). All methods were carried out in accordance with relevant guidelines and regulations. The original protocol was retrospectively registered with the DRKS , which meets the International Committee for Medical Journal Editors’ (ICMJE) clinical trial registration requirements .For the randomization protocol, two types of identical envelopes were created. The envelopes contained a card with a printed “A”  or “B”  stamp, respectively. Following a simple randomization protocol, an enrolling clinician (NA) presented participants with a box from which an envelope was drawn. The enrolling clinician was blind to the drawn intervention. Following this allocation procedure, participants met with a Terzo employee, handed over the envelope, and the respective trial protocol and procedures were explained. Randomization was continued until the target 1; DIG: wait], post-treatment/pre-treatment , follow-up/post-treatment , and follow-up [DIG: t3]  at 55.91 dB (SD = 19.24).Prior to study inclusion, participants’ hearing ability was tested using pure tone audiometry (PTA). Here, participants indicated the quietest detectable sound (dB) at several points across the frequency range . Right-sided tinnitus perception was reported by 15 participants (8.5%); left-sided by 31 participants (17.5%), and bilateral by 131 participants (74%). Pure (sinus) tone perception was reported by 121 participants (68.4%) and narrow-band noise by 54 participants (30.5%). The average reported tinnitus frequency was 5.98 kilohertz  tinnitus, (2) the mechanisms of tinnitus onset and the relationship between tinnitus and hearing loss, as well as (3) principles and methods of treatment with hearing aids. In addition, subjects were prepared for their acoustic impressions when wearing hearing aids in order to improve the acceptance of hearing aid amplification. All participants underwent binaural hearing aid fitting and, subsequently, completed the auditory training. Hearing aid fittings were adjusted to subjects’ individual levels of hearing loss. Because the present sample included participants with mild-to-moderate hearing loss , fittings were based on the Desired Sensation Level (DSL), v5 child’s formula to maximize speech audibility across a variety of real-world settings ,37. Ear Following a one-week adjustment period, participants were instructed to independently practice a standardized training intervention for approximately 1 h/day over a period of 14 days. The training intervention comprised a combination of auditory materials (CD) and daily, workbook-based exercises aimed to improve speech-comprehension-in-noise. The exercises included comprehension tasks pertaining to numbers, texts, similar-sounding words, syllables, and required mnestic as well as concentration elements. Thematic blocks were labelled (1) speech comprehension with and without noise, (2) concentration, (3) acoustic retention, (4) semantic memory, and (5) acoustic crossword puzzles. The training manual featured a variety of sequential exercises that were linked to specific days of the intervention period. Participants could record their progress in daily protocol sheets.The present paper reports the effects of Terzo© hearing therapy on tinnitus-related distress and psychological wellbeing. Training intensity was quantified using participants’ self-reports obtained at the post-treatment timepoint as well as the hearing aids’ automated usage recordings. At the end of the intervention (post-treatment), participants returned the training CD. Hearing aids and self-instruction materials were returned at follow-up.total = 0.94).The German version of the Tinnitus Questionnaire (TQ) by Goebel and Hiller  assessestotal = 0.94).The Tinnitus Handicap Inventory .The Tinnitus Functional Index .Subjective stress was measured using the Perceived Stress Questionnaire (PSQ ). The scanxiety = 0.85; αdepression = 0.90).The Hospital Anxiety and Depression Scale (HADS) is a screening instrument for self-reported anxiety and depression  .The ICD-10-Symptom-Rating (ISR ) is a qu1-t2 vs. DIGwait-t1] as within factor and “tinnitus-related distress” , “perceived stress” [PSQ], or “psychological epiphenomena”  as dependent variables. Cohen’s d quantified significant effects where indicated . Step 2: In order to investigate the stability of the identified treatment effects, separate three-tiered repeated-measures ANOVAs were conducted on the significant outcome measures identified in Step 1. For these analyses, data for the IIG and DIG were pooled (n = 150). Pooling was possible because computations revealed that [a] the IIG and DIG did not differ on any of the defined outcome variables at their respective pre-treatment timepoint [t1], [b] there were no significant “group” [IIG vs. DIG] × “time” interaction effects for any of the outcome measures when considering all three treatment-related measurement timepoints , and [c] there were no significant covariate effects of previous hearing aid use or hearing aid use during treatment. Where significant, age or hearing ability (PTA) were included as covariates. Post hoc paired-samples t-tests investigated between-timepoint differences, given a significant main effect of time. Again, Cohen’s d quantified effect sizes. All reported results did not differ for participants with or without previous hearing aid use. See Sociodemographic information was summarized using descriptive statistics. As expected, given the stratification and randomization protocol, the IIG and DIG did not differ on age, gender, and previous use of hearing aid use at pre-treatment. Step 1: Separate two-way analyses of variance (ANOVA) investigated the effects of Terzo© hearing therapy on [a] tinnitus-related distress, [b] perceived stress, and [c] psychological epiphenomena. We specified “group” [IIG vs. DIG] as between factor, “time”  perceived stress, [ISR-measured] anxiety-, depression-, obsession-, somatoform-, and eating-related symptoms, as well as [HADS-measured] anxiety- and depression-related symptoms. By contrast, [ISR-measured] overall psychological epiphenomena levels showed mild elevation.SD = 4.08). Participants who previously wore hearing aids did not differ in their hearing aid use from the remaining subjects .Participants in the IIG used the hearing aids for 9.33 h/day  = 21.21, p < 0.001, d = −0.304 [small effect]; THI: F = 5.02, p = 0.026, d = −0.137 [negligible effect]); and TFI: F = 34.40, p < 0.001, d = −0.525 [medium effect]). There were no significant interaction effects for perceived stress and psychological epiphenomena; however, significant main effects of time emerged for anxiety and emotional distress . See Significant “group” × “time” interaction effects emerged for all three tinnitus questionnaires. Relative to the DIG that yielded stable measurements, the IIG showed significant improvements of tinnitus-related distress  = −0.48, not significant). The three-tiered rmANOVAs  confirmed significant improvements in tinnitus-related distress  = 49.75, p < 0.001, d = −0.363 [small effect]; THI: F = 23.61, p < 0.001, d = −0.268 [small effect]; TFI: F = 84.61, p < 0.001, d = −0.570 [medium effect]). As hypothesized, post hoc comparisons revealed significant improvements from pre- to post-treatment and pre-treatment to follow-up with no significant differences between post-treatment and follow-up. Pre-to-follow-up TQ change comprised 5.8 (SD = 8.2), THI change 4.9 (SD = 10.9), and TFI 12 (SD = 14.6) points. In the context of the overall mild rates of tinnitus-related distress, clinically relevant change  was obtained for 0.7 (TQ), 10.7 (THI), and 2.7% (TFI) of participants, respectively. See The stability of treatment-related effects was investigated in the pooled dataset . Terzo-fitted hearing aids were used for 9.49 h/day during the follow-up period  = 5.98, p = 0.003, d = −0.152; PSQ_t: F = 5.07, p = 0.009), d = −0.165; and PSQ_d: F = 3.70, p = 0.029, d = −0.122) and emotional distress, notably depressive symptoms and anxiety  = 4.30, p = 0.014), d = −0.080; HADS_a: F = 4.50, p = 0.012), d = −0.110; ISR_total: F = 3.92, p = 0.023, d = −0.109; ISR_d: F = 3.90, p = 0.025, d = −0.115; and ISR_sup: F = 3.79, p = 0.029, d = −0.100). Whilst statistically significant, the effect sizes for these changes were ‘negligible’ (<0.2). See Significant, yet uncontrolled, pre- to follow-up changes emerged for indices of perceived stress  emerged between participants’ hearing ability and emotional distress , as well as depression . No correlations were found between PTA indices and change across those psychological variables that were found to improve over time.At pre-treatment [IIG: tThe present study investigated the effects of Terzo© hearing therapy on tinnitus-related distress and accompanying psychological parameters. The intervention combined binaurally-fitted hearing aids with a 14-day, CD-enhanced Terzo self-study program.Using a randomized-controlled cross-over design, an immediate (vs. delayed) intervention group showed significantly greater improvements in tinnitus-related distress. This finding demonstrates for the first time that the 14-day Terzo© hearing therapy bears the potential to improve self-reported psychological aspects of tinnitus symptomatology in patients with chronic tinnitus and mild-to-moderate high-frequency hearing loss. Importantly, however, the effects sizes of the observed effects differed according to the respectively used questionnaire  highlighting the importance of matching the content and targets of interventions with respectively applied measurement choices .The study joins previous research on self-reported symptom-relief following hearing aid fittings in patients with hearing loss ,20,47 wiBecause the intervention primarily aimed to improve executive and attention-related processes in their interaction with participants’ hearing ability, it follows that the observed improvements were primarily reflected in the TFI, which, unlike the TQ and THI, emphasizes audiological and functional aspects of chronic tinnitus ,53.Whilst the Terzo training was not directly aimed at addressing psychological parameters, we expected indirect psychological benefits, possibly through ameliorating sensory contributions that have been well established in their impact on emotional distress . ContrarExamining treatment effects within the pooled sample, the improvements of tinnitus-related distress remained stable at follow-up. Stable improvements following hearing-focused interventions have been previously reported after cochlear implantation ,70,71,72Finally, exploratory analyses revealed statistically significant, yet negligible, improvements of perceived stress and emotional distress indices between pre-treatment and follow-up that were further unrelated to participants’ hearing ability.Participants in the present study yielded only mild levels of hearing impairment and tinnitus-related, as well as broader psychological distress. Future studies need to investigate the helpfulness of the approach for more severely impaired populations that were excluded in the present study. Moreover, a Terzo employee conducted the hearing aid fittings and the explanatory introduction to the hearing therapy. Whilst this may constitute a source of bias, it is transparently highlighted in the study’s Conflict of Interest section, and all data collection and analysis procedures were conducted independently. Terzo© hearing therapy consists of a combination of hearing aid fitting and auditory training. Future studies might wish to investigate the specific effects of the hearing aids or auditory training components in order to maximize the effects for different subgroups of patients at various levels of distress or (hearing) impairment.The present study offers the first support of the hypothesis that a combination of binaural hearing aid fittings and auditory training (the Terzo© hearing therapy) can improve tinnitus-related distress in patients with chronic tinnitus and mild-to-moderate hearing loss. Whilst methodologically exploratory, the observed benefits of this intervention on psychological indices warrant further investigation, particularly across samples with varying levels of emotional distress.


Face masks are mandatory during the COVID-19 pandemic, leading to attenuation of sound energy and loss of visual cues which are important for communication. This study explores how a face mask affects speech performance for individuals with and without hearing loss. Four video recordings  were used to examine individuals’ speech performance. The participants completed a listen-and-repeat task while watching four types of video recordings. Acoustic characteristics of speech signals based on mask type  were also examined. The availability of visual cues was beneficial for speech understanding—both groups showed significant improvements in speech perception when they were able to see the speaker without the mask. However, when the speakers were wearing the mask, no statistical significance was observed between no visual cues and visual cues conditions. Findings of the study demonstrate that provision of visual cues is beneficial for speech perception for individuals with normal hearing and hearing impairment. This study adds value to the importance of the use of communication strategies during the pandemic where visual information is lost due to the face mask. Hearing loss, as the name indicates, is the loss of hearing and it can be caused by various factors, such as noise exposure and ototoxic drugs. Depending on one’s hearing characteristics, hearing loss is typically managed by hearing devices, such as hearing aids (HAs) and cochlear implants. A HA is a sound amplifying device that is programmed by a hearing healthcare professional. The HA optimization process involves one’s audiometric data as well as communication needs . For exaWith the recent pandemic, the importance of visual cues has been heightened even more. The use of face masks and social distancing have been mandated, leading to communication challenges. Face masks, as multi-layered fabrics, can reduce sound energy, especially mid-to-high frequency ,11. In BParticipants who met the following criteria were enrolled in the study: (a) native Korean speakers and (b) adults (19 years and above). With the inclusion criteria, a total of 25 adult participants, who were native Korean speakers, were enrolled in the study. The age range of the participants was from 19 to 69 years old. The mean age of the NH group was 24.6 years (SD = 3.3) while the mean age of the hearing impaired (HI) group was 58.0 years (SD = 11.8). Among the 25 participants, 14 of them had NH and 11 had bilateral moderate sensorineural hearing loss with an asymmetry in hearing thresholds below 10 dB across testing frequencies . The NH group’s puretone averages were 3.2 dB in the right ear and 2.4 in the left ear. The HI group had puretone averages of 42.5 dB in the right ear and 43.6 dB in the left ear. Individuals who were unable to watch TV at a distance of 1 m and those with middle ear pathology and neurological and mental disorders were excluded from the study. All experimental procedures were approved by Samsung Medical Center’s Institutional Review Board. An informed consent document was obtained from the participants. Informed consent was also obtained from speakers to publish the images in an online publication.Conventional pure-tone audiometry was performed in a sound booth using an AudioStar Pro  audiometer and insert earphones.A total of four video recordings were created: a female native Korean speaker with and without a face mask and a male native Korean speaker with and without a face mask . The masUsing the Knowles Electronics Manikin for Acoustic Research (KEMAR), which is a manikin used for audiological research, the sound pressure level of speech signals was measured in three conditions: no mask, surgical mask, and N95. Audio recordings of the videos (List 1 only) were presented through a loudspeaker that was placed 1 m away. The surgical and N95 masks were placed around the loudspeaker for the surgical and N95 conditions, respectively.The speech testing was conducted using the video recordings in a semi-anechoic chamber. The participants were asked to repeat target sentences that were presented through a loudspeaker at 50 dBA. The loudspeaker was placed 1 m away from the participant. The number of accurately repeated sentences was calculated to determine percent-correct scores. Using the four video recordings, the participants completed the following test conditions: no mask and no visual cues, no mask and visual cues, mask and no visual cues, and mask and visual cues. The video recordings were displayed on a monitor and the monitor was turned off for the no visual cues condition. The test conditions were randomized for each participant. The testing took an hour and breaks were given as needed.Using the Statistical Package for the Social Sciences (SPSS) version 26 , the Wilcoxon-signed rank test was performed to analyze the differences between the mask and unmask conditions as well as no visual cues and visual cues conditions for NH and HI groups. Non-parametric tests were used as our results did not pass the normality test.p < 0.001) and between no mask and N95 conditions (p < 0.001)—when the speakers were wearing the surgical and the N95 mask, the sound pressure levels were significantly reduced. The maximum sound attenuation occurred at 2560 Hz (8.2 dB) between the no mask and the surgical conditions and at 1798 Hz (7.5 dB) between the no mask and the N95 conditions for the female speaker. For the male speaker, the amount of sound attenuation was the greatest at 4593 Hz (7.2 dB) between the no mask and the surgical conditions and at 1816 Hz (6.8 dB) between the no mask and the N95 conditions.The amount of sound attenuation based on mask type was examined for both speakers . For thep = 0.007 for the NH group and p = 0.005 for the HI group). However, no significant differences were observed between the two conditions for both groups in the mask condition (p = 0.120 for the NH group and p = 0.391 for the HI group).Differences in the speech performance between the NH and HI groups are illustrated in p = 0.006 for the NH group and p = 0.004 for the HI group) for both groups. Face masks, however, did not have any impact on speech understanding when visual cues were unavailable (p = 0.812 for the NH group and p = 0.632 for the HI group) for both groups.The impact of face mask on speech understanding was also investigated . In the In our study, when the speakers were not wearing a face mask, speech recognition improved with the provision of visual information regardless of the presence of hearing loss. However, when the speakers were wearing the face mask, provision of visual cues did not have any significant impact on speech performance for both groups. In a case where visual cues were not available, wearing a face mask had a significant impact on speech understanding, but no statistical significance was observed between the mask and no mask conditions when visual cues were available to the participants. The findings are in line with previous studies to some extent that the availability of visual information is beneficial for communication—the participants showed better speech performance even if the speakers were wearing a face mask ,9,16,17.Findings of this study are meaningful as they add value to the use of communication strategies. As mentioned earlier, the loss of visual cues with the face mask could lead to communication difficulty and in medical settings, in particular, communication challenges could interfere with the delivery of patient-centered care ,24,25,26


The ongoing COVID-19 pandemic has quickly become a health threat worldwide, with high mortality and morbidity among patients with comorbidities. This viral infection promotes the perfect setting in patients for the development of opportunistic infections, such as those caused by fungi. Mucormycosis, a rare but deadly fungal infection, has recently increased its incidence, especially in endemic areas, since the onset of the pandemic. COVID-19-associated mucormycosis is an important complication of the pandemic because it is a mycosis hard to diagnose and treat, causing concern among COVID-19-infected patients and even in the already recovered population. The risk factors for the development of mucormycosis in these patients are related to the damage caused by the SARS-CoV-2 itself, the patient’s overstimulated immune response, and the therapy used to treat COVID-19, causing alterations such as hyperglycemia, acidosis, endothelial and lung damage, and immunosuppression. In this review, the molecular aspects of mucormycosis and the main risk factors for the development of COVID-19-associated mucormycosis are explained to understand this virus–fungi–host interaction and highlight the importance of this neglected mycosis. In late 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19), was firstly associated with human disease .Like in other viral diseases, secondary infections are important COVID-19 complications, which might be caused by other viruses, bacteria, protozoa, and fungi . At the Mucorales order [COVID-19-associated mucormycosis (CAM) is a severe emerging systemic fungal infection caused by several species of the es order , and it es order ,9,11,12.es order ,26,27,28In this review, we will explain the molecular aspects of mucormycosis and discuss CAM’s main physiopathological characteristics and the fundamentals of its development to understand this pathogen–host interaction.Mucormycosis, previously known as zygomycosis, is a rare opportunistic, invasive, and deadly fungal infection that has increased in incidence in the last few years, as a secondary infection in patients with debilitating diseases, such as diabetes, cancer, and organ transplantation, and during natural disasters, such as tsunamis and earthquakes . DespiteAlthough precise data about the prevalence of this mycosis are unknown, due to the lack of diagnosis, according to epidemiological data of autopsy reports on invasive fungal diseases from 2008 to 2013, the etiological agents of mucormycosis were the fourth most common cause of invasive mycoses in the general population and the third most common cause in the onco-hematological and stem cell transplant populations, with a high prevalence of severe cases (around 70%) . This inThe transmission route for these fungi can be through spores inhalation, contaminated food ingestion, traumatic inoculation with contaminated materials, or implantation in already abraded skin ,35, whicMucorales order, under the subphylum Mucormycotina and the phylum Glomeromycota [Rhizopus is the genus most frequently associated with the disease, followed by Mucor and Lichtheimia, while Zygomycetes genera, including Saksenae, Cunninghamella, Apophysomyces, and Rhizomucor, are less common [The mucormycosis causative agents are fast-growing thermotolerant fungi belonging to the romycota ,40. Rhizs common ,40,41. Ts common ,38,42. Ms common ,44 and rs common ,36.Mucorales share many unique characteristics, there are important differences among species in their epidemiology, pathogenesis, virulence, susceptibilities to the host immune response and antifungals, disease severity, and outcome [Rhizopus oryzae, which is the most common mucormycosis causative agent [Although all  outcome ,46,47. Hve agent .-Conditions that cause decreased numbers of phagocytes and altered immune functions, including hematologic malignancies, hematopoietic stem cell transplantation, solid organ malignancies and transplantation, and rheumatological diseases ,40,42,49-Uncontrolled diabetes, diabetic ketoacidosis, and metabolic acidosis, which are conditions that cause changes in pH and iron availability within the host ,42,49,51-The use of corticosteroids/immunosuppressors in high doses and for long periods ,42, chel-Malnutrition and neonatal prematurity ,49. On t-Traffic and home accidents, trauma, skin injuries, and burns ,32,33,41-Natural disasters, such as tsunamis, tornadoes, and volcanic eruptions ,34,41,53-The use of contaminated medical materials, such as bandages and tongue depressors, and prolonged hospital stays ,34.As mentioned before, these fungi are ubiquitously found in the environment, and their ability to cause disease in immunocompetent hosts is anecdotic but possible . In the Mucorales have many traits that contribute to their ability to cause such an aggressive disease, including thermotolerance [olerance ,55, rapiolerance ,56, cellolerance ,36,57, aolerance , downregolerance ,59, and olerance .Mucorales virulence factors that participate in the infection process are the attachment to endothelial cells and iron uptake. Mucorales are vasotropic; therefore, the interaction between the fungus and endothelial cells around blood vessels is an indispensable step in mucormycosis pathogenesis [The fungus might enter the host through different vias, including spore inhalation, skin inoculation, or ingestion through the gastrointestinal tract . Indepenogenesis ,40, whicRhizopus, Mucor, and Lichtheimia, have three to seven CotH copies expressed, while low-virulent genera, such as Apophysomyces, Cunninghamella, Saksenaea, and Syncephalastrum, express only one to two copies, and Entomophthorales isolates, previously considered close to Mucorales, have no CotH genes and are avirulent [Once in the host, spores attach to the basement membrane extracellular matrix proteins, laminin and collagen IV, and secrete proteolytic enzymes ,62,63, svirulent .Mucorales order since other opportunistic pathogens, such as Candida albicans and Aspergillus fumigatus, do not bind this endothelial cell receptor [Mucorales binding to the host’s cells since blockage or suppression of GRP-78 does not completely abolish endothelial invasion [Rhizopus delemar, R. oryzae, and Mucor circinelliodes [Mucorales-mediated endothelial damage in vitro [The GRP-78 recognition by CotH proteins causes host cell death by the induction of endothelial cell-mediating endocytosis, initiating the fungal invasion of the endothelium . The expreceptor . Howeverinvasion . In thiselliodes , also coin vitro .Mucorales, iron uptake is performed by three mechanisms: low molecular weight iron chelators or siderophores, high-affinity iron permeases, and heme-oxygenases [R. oryzae growth and causing phagocytosis defects [Rhizopus is capable of using external siderophores, such as DFO, an iron chelator used as a treatment in patients with increased iron overload [R. oryzae expresses FTR1, which, when inhibited or reduced, causes fungal virulence reduction [When talking about fungal growth and replication, nutrition is a very important factor, and iron is essential for these processes. In ygenases ,36. In h defects ,69. In h defects  while in defects ,70. Unde defects , and the defects ,72 that, defects , which ioverload . DFO cheoverload ,74, reoxoverload ,72. The overload . FTR1 peeduction . Mucorales, to which they have access due to their angioinvasive ability [Finally, hemoglobin can also be used as a source of ferric iron by  ability . Once th ability ,57,72. I ability .Mucorales spores germination and dissemination are innate immune cells, consisting of circulating neutrophils, mononuclear cells, and macrophages [R. oryzae spores and inhibiting their germination, macrophages cannot kill them due to the inhibition of LC3-associated phagocytosis (LAP), an important antifungal pathway that participates in the host defense regulation [Rhizopus spore cell wall blocks phagosome responses, completely inhibiting phagosome maturation and allowing fungal intracellular persistence [Mucorales virulence, prolonging fungal survival in the lungs and serving as transport of spores to other organs [Mucorales seem to be dependent on the spore wall composition [Rhizopus recognition by neutrophils [The main host defense against the rophages . Tissue rophages ,75,76,77gulation . It was r organs ,79. Therr organs ,80. In aposition , and theMucorales spores and hyphae. Once the platelets bind the pathogen and are activated, they damage hyphae in a time-dependent manner through the secretion of granules with pro- and anti-inflammatory cytokines and chemokines with antifungal properties [Platelets also participate in the host immune response during this infection, as they strongly bind to operties ,81 as weoperties ,77,81. Ioperties . Additiooperties .Mucorales. It has been observed that NK cells are activated by R. oryzae hyphae and damage this morphology, mainly by the protein perforin [R. oryzae hyphae with these cells decreases secretion of IFNγ and RANTES , which are important molecules that improve the fungicidal activity of macrophages and the host defense against fungi [Natural killer (NK) cells are also considered to have an important role in the immune response against perforin ,85 and dperforin . Howeverst fungi ,86. TherMucorales are capable of down-regulating genes involved in pathogen recognition, innate immune responses, and tissue repair mechanisms, facilitating fungal growth [It has been demonstrated that l growth .Mucorales is scarce, it is already known that greater resistance to pulmonary mucormycosis is associated with an early Th-1 response, mediated by IFNγ and IL-2, while the infection control is mediated by the Th-17 response, with increased production of IL-17 and IL-2 by the spleen [Although the knowledge regarding the adaptative response against e spleen . Just lie spleen .Mucorales. It has been widely reported that hyperglycemia causes phagocyte dysfunction [Finally, the patient’s health conditions, such as diabetes and acidosis, alter the immune response against function  and suppfunction , while kfunction ,59,65, aMucorales species have different drug resistance profiles. The main antifungals used for the treatment of this mycosis are amphotericin B, posaconazole, isavuconazole, and itraconazole, and they have different responses against the major agents of human infection, including Lichtheimia spp., Rhizopus spp., Cunninghamella spp., and Mucor spp. [Mucorales species is amphotericin B, with low minimum inhibitory concentrations (MICs) in vitro; however, higher MICs have been reported for this drug against Cunninghamella spp. and Rhizopus spp. [Mucorales and highly dependent on the species, with higher MICs in vitro than amphotericin B; however, in vivo studies have demonstrated that azoles can be active against these pathogens: itraconazole can be effective against Rhizomucor, Syncephalastrum, and Absidia, but its effect is limited against Cunninghamella spp. and Mucor spp.; posaconazole has good effectivity against Absidia spp. and Mycocladus corymbifera but needs higher MICs for Rhizopus spp. and Cokeromyces recurvatus; and isavuconazole has partial in vitro activity against most Mucorales except for Mucor circinelloides [Mucorales, such as Mucor spp., Rhizopus spp., Absidia spp., Cunninghamella spp., and Syncephalastrum spp. [Mucorales species in vitro but are thought to be a good option when used in combination with other drugs [Proper mucormycosis treatment depends on the etiological agent since the different cor spp. . The mospus spp. ,94,95,96elloides ,98. In trum spp. . Echinocer drugs .Combined therapy, such as antifungals plus surgical intervention, is usually related to a better mucormycosis outcome ,100,101.Liposomal amphotericin B is the first-line antifungal monotherapy for the treatment of mucormycosis with the involvement of various organs , but difAzoles such as posaconazole and isavuconazole are also considered first-line treatments . IsavucoMucorales species, a combination that might be used as good salvage therapy [Mucorales species can be observed. For this, a combination of liposomal amphotericin B and either posaconazole or voriconazole can be used [Evidence in animal models suggests that antifungal combination therapy can improve disease outcomes and survival rates . Posacon therapy ,118,119. therapy ,120,121. be used ,123. The be used .M. irregularis in patients with no underlying diseases and intolerance to amphotericin B [In the cases of refractory mucormycosis or toxicity to first-line therapy, some salvage treatments can be used. Itraconazole alone has been used to treat cutaneous mucormycosis caused by ericin B  and, in ericin B . As already mentioned, the use of iron chelators such as deferoxamine is associated with a higher risk to develop this mycosis and a worsening of the disease, but newer iron chelators, such as deferiprone and deferasirox, have been successfully used to treat experimental mucormycosis .Rhizopus T cells from healthy donors show reactivity against Mucorales and enhance the phagocyte killing effect [Rhizopus hyphal damage [In addition, immunotherapy strategies have also been used for the control of mucormycosis since anti-g effect ,126. In l damage . A combil damage .Although the first report of mucormycosis in the literature dates from 1855 , and desThe increase in CAM development has been mainly observed during the second wave of the COVID-19 pandemic, which might suggest a more effective association between mucormycosis and the SARS-CoV-2 delta variant, probably because it is more contagious and resistant to vaccines, with a higher risk of hospitalization and predisposition for the rhino-cerebral form, and also because of this variant’s ability to affect the pancreas, predisposing to hyperglycemia .The majority of CAM cases reported worldwide are from India, followed by the United States, Egypt, Iran, Brazil, and Chile, and a few cases have also been reported in the United Kingdom, France, Italy, Austria, and Mexico . Rhizopus spp. [According to epidemiological reports, it has been observed that, just like COVID-19, CAM is mainly present in male patients with diabetes, hypertension, or treated with glucocorticoids ,140,141.pus spp. ,135,141.CAM has been reported in patients with active SARS-CoV-2 infection but also in patients already recovered, and although the majority of CAM cases were reported in severe COVID-19 patients, the mycosis has also been found in mild/moderate SARS-CoV-2 infections . The firHyperglycemia, caused by the use of corticosteroids to treat COVID-19  and dysrLow pH, caused by diabetic ketoacidosis or metabolic acidosis caused by corticosteroid use , which rImmunosuppression, caused by SARS-CoV-2 infection and hypoxia, corticosteroids, and tocilizumab use ,149 or pFree iron availability, caused by hyperglycemia, the COVID-19 cytokine storm, or by acidosis. Hyperglycemia and diabetic ketoacidosis cause dissociation of iron from ferritin and lactoferrin, thus elevating free iron concentrations , and somPulmonary changes, including vascular endothielitis, thrombosis, and angiogenesis, caused by SARS-CoV-2 infection, which provides a focal point for fungal growth and dissemination ,160. TheOverexpression of endothelial cells GRP-78, caused by hyperglycemia, acidosis, and iron availability, which enables angioinvasion, hematogenous dissemination, and tissue necrosis ;Dysregulation of ACE2 by SARS-CoV-2. By being present in many organs and tissues, the alteration of the receptor ACE2 expression causes a suitable environment for the development of mucormycosis. During COVID-19, a downregulation of ACE2 has been observed in the lungs , which cProlonged hospital stays and mechanical ventilation in severe COVID-19 cases expose the patient to fungal coinfections ,103.To cause such an aggressive and lethal infection, the causative mucormycosis fungi take advantage of the many alterations that SARS-CoV-2 infection generates on the host, such as :HyperglyIn addition, the use of industrial oxygen in COVID-19 patients due to a shortage of medical oxygen and the re-use of oxygen masks is suggested to be related to the development of CAM, especially in third-world countries. Unlike medical oxygen, industrial oxygen is not purified nor stored in disinfected cylinders ,162.In patients with the rhino-orbital/cerebral form, the most commonly observed symptoms are orbital/facial pain and edema, followed by loss of vision, nasal blockage, and ptosis . These pIn patients with pulmonary involvement, the most common symptoms are fever, cough, dyspnea, and hypoxia, and radiographic findings might include consolidations, cavitary lung lesions, and bronchopleural fistula formations with empyema ,16,168.Both the European Confederation of Medical Mycology (ECMM) and the Mycoses Study Group Education and Research Consortium have released a detailed guide to facilitate mucormycosis diagnosis and treatment , while tMucorales grow in these media in 2 to 7 days [Mucorales can be misidentified as Aspergillus spp. [The gold standard for mucormycosis diagnosis is culture and microbiological or histopathological examination of tissues from different lesions ,145,170.o 7 days . Histopao 7 days . Howevero 7 days ,174. In lus spp. . In addilus spp. . For pulmonary mucormycosis, radiological features can be suggestive of the infection, but these are non-specific and can overlap with other fungal cases of pneumonia or COVID-19. A pulmonary CT scan can be used for the detection of the reverse halo, which is observed as ground-glass opacity surrounded by a ring of consolidation mainly in the peripheral locations of the lungs . HoweverFTRI [Mucor, Rhizopus, Lichtheimia, and Rhizormucor [Mucorales species, which can also be distinguished from aspergillosis [Other techniques, such as conventional and quantitative PCR (polymerase chain reaction) targeting the internal transcribed spacer (ITS) , semi-neFTRI ,188,189,FTRI . PCR teczormucor ,190,191,zormucor . PCR comzormucor ,192. In zormucor ,194,195.gillosis . HoweverMucorales, proving to be highly sensitive for the diagnosis of invasive murine mucormycosis [Currently, there are no serological diagnostic methods for mucormycosis , but somrmycosis .Mucorales species, such as the ID32C and API 50CH kits, that successfully identify species such as Lichtheimia corymbifera, Lichtheimia ramosa, and Rhizomucor pusillus [Mucorales species that cause mucormycosis and have shown high variability in the assimilation patterns among R. oryzae isolates [Some carbon assimilation commercial kits are available for the identification of the pusillus ,200. Howisolates .Therefore, diagnosis of CAM mostly relies on conventional culture and histopathological demonstration, which is time-consuming and with low sensitivity, delaying diagnosis and treatment .A metanalysis of published cases of CAM suggests that this infection is associated with high morbidity and mortality, mainly due to late diagnosis . This stThe therapy approach for the management of CAM is similar to that of mucormycosis, and the early diagnosis is essential for a good outcome ,169. TheMucorales [Due to the limitations of antifungal drugs, which include side effects and optimal dosage, nanosystems have been used for the delivery of amphotericin B via oral, topical or pulmonary routes with promising results . In thesucorales .When CAM is being treated during active SARS-CoV-2 infection, potential drug-drug interactions of antifungals, antivirals, and immune therapies need to be addressed. For example, the administration of amphotericin B with steroids can cause hypokalemia in the patient, complicating the disease .Mucor racemosus, and gluvastatin and rosuvastatin, which have fungicidal effects against Rhizomucor and Rhizopus spp. [R. arrhizus than amphotericin B monotherapy [As new treatments are being tested for CAM, statin therapy has been suggested . Statinspus spp. . Moreoveotherapy .R. delemar damage of alveolar epithelial cells in mice with diabetes ketoacidosis infected with pulmonary mucormycosis [In addition, anti-CotH3 and CotH7 antibodies have been found to protect mice with neutropenia and diabetes ketoacidosis against mucormycosis , while armycosis .Mucorales in vitro [The use of hyperbaric oxygen has been proven beneficial as a possible adjunctive treatment, especially in patients with diabetes , due to in vitro .Mucorales, it has been demonstrated in candidiasis and other fungal infections [Probiotics, due to their anti-inflammatory activity and antifungal and anti-mycotoxigenic activities ,214,215,fections ,218,219 fections ,223,224.Mucorales, it has been proven they have in vitro and in vivo antimycotic activity against Candida albicans, Candida glabrata, Trichophyton spp. [Aspergillus niger [A treatment being proposed for COVID-19 and some fungal infections that is gaining popularity are retinoids or vitamin A. Retinoic acid, the retinol biologically active metabolite, regulates many mechanisms in the host, including inflammatory effects, innate and adaptative immune responses, cell proliferation and differentiation, antiviral effects, and angiogenesis ,226,227.ton spp. , and Aspus niger , for whiMucorales agents [R. oryzae, which has shown a strong therapeutic action against Rhizopus spp., as observed by the increased survival rates of neutropenic mice with mucormycosis [Rhizopus infection in immunosuppressed mice [Mucorales, including Rhizopus spp., and inhibits the final step of heme biosynthesis [Drugs in the preclinical investigation, such as VT-1161, APX001A, and hemofungin, have been suggested as potential anti-s agents . VT-1161rmycosis ,238; APXsed mice ; hemofunynthesis .-During COVID-19 management, hyperglycemia should be strictly controlled;-Corticosteroid therapy should only be used in patients with severe SARS-CoV-2 infection, for short periods and at low doses, just like other drugs that target the immune response, such as tocilizumab ;-Mucorales should be limited as much as possible by using face masks and avoiding being outdoors;The patient’s exposition to -Mass vaccination against COVID-19 can also help to reduce the chance to develop severe secondary complications .The occurrence of CAM can be reduced up to a certain point, following several steps as suggested by :-During Even with treatment, CAM morbidity and mortality is high, being about 40–50% in prevalent regions and 50–100% in non-prevalent regions ,241, butThe recent rise of the COVID-19 pandemic has highlighted the importance of mucormycosis worldwide. The lack of knowledge about mucormycosis and its etiological agents has complicated CAM diagnosis, treatment, and prevention and therefore has worsened the clinical management of COVID-19 patients, affecting health and the economy globally. Many efforts have been made to understand SARS-CoV-2 and to prevent and treat COVID-19, but the study of fungal coinfections, such as mucormycosis, is a priority for both basic and clinical research.Mucorales needs to be addressed urgently. For example, neither molecular nor serological diagnosis methods are commercially available for the daily and rapid identification of this mycosis, which hinders diagnosis and delays treatment. Future efforts should be made in finding fungal antigenic molecules and host antibodies generated against them, developing fast and accessible molecular and serological diagnostic methods, and also in finding molecular markers for the identification of the mucormycosis etiological agents. The different antifungal resistance profiles of Mucorales species highlight the importance of fungal identification at the species level. Moreover, research in new antifungal therapies is needed to improve the infection outcome and decrease the mortality rate. As mentioned before, the typical antifungal drugs currently used have different responses depending on the etiological agent and are usually not very effective for severe cases if administrated out of time. Moreover, since they have to be used in high doses and for long periods, they can be toxic, permanently damage organs, and can generate resistance. In addition, the shortage of these drugs in regions where mucormycosis is endemic is of concern since it limits the treatment of many patients with severe forms of mycosis. Therefore, due to the lack of rapid and accessible diagnosis, treatment for mucormycosis can be challenging. One alternative to overcome these hurdles is to focus future research efforts on drug repurposing, looking for already known drugs with undiscovered antifungal activity.To improve the current global crisis, the study of opportunistic pathogens such as There is not much that can be done to prevent CAM; simply, certain measures can be taken, such as avoiding mucormycosis risk factors, which can be complicated for patients with underlying diseases and in regions with poor healthcare systems. Therefore, we conclude that research efforts in mucormycosis are as important as those in COVID-19 to fight the current pandemics and associated infections.


The FAO/WHO/UNU (1985), FAO/WHO/UNU (2004), Harris–Benedict, and Mifflin–St Jeor equations overestimated the RMR IC by 283.2, 311.2, 292.7, and 203.0 calories/day and by 296.7, 413.8, 280.0, and 176.6 calories/day for women with overweight and obesity (p < 0.001), respectively. The Harris–Benedict adjusted weight (0.5) equation underestimated RMR IC by 254.7 calories/day. The predictive equations overestimated RMR IC in women with excess body fat. The Mifflin–St Jeor equation showed less overestimation and better adequacy, but was not exempt from inaccuracy.Underestimating/overestimating resting metabolic rate (RMR) affects energy prescription. The objective was to compare RMR by indirect calorimetry (RMR IC) and RMR estimated by predictive equations in women with excess body fat. This was an analytical cross-sectional study with 41 women aged 18–28 with overnutrition according to body composition. The RMR IC was measured and RMR estimated using the FAO/WHO/UNU (1985), FAO/WHO/UNU (2004), Harris–Benedict, and Mifflin–St Jeor equations. The percentage of adequacy (90–110%), overestimation (>110%), and underestimation (<90%) were evaluated for RMR IC. Data were described by percentiles because of non-normal distribution according to the Shapiro–Wilk test. The Kruskal–Wallis test and Bland–Altman analysis were applied at a significance level of α < 0.05. The RMR IC was 1192 and 1183 calories/day ( Total energy expenditure consists of three principal components, which are the basal metabolic rate (BMR), the thermic effect of food, and physical activity . The BMR2) and carbon dioxide (CO2) concentrations in the expired air [The RMR must be estimated in a nutritional dietary intervention to prescribe an ad-equate diet in terms of calories and nutrients. There are various methods to measure RMR, and indirect calorimetry (IC) is considered as the gold standard . Howeverired air .In routine clinical practice, RMR is estimated using different predictive equations, which have proven to be easy to use, cost-free, and always available. They are derived from regression models that include sex, age, anthropometric measurements (weight and height), and body composition (lean body mass and body fat) variables. Among the most used equations are the Harris–Benedict , FAO/WHOThe accuracy of the predictive equations is determined by the individual’s nutritional status. Predictive formulae have been less accurate in adults with excess body fat . SeveralIt should be noted that there are few studies on this topic, especially in Latin America. The purpose of the study was to determine the most accurate predictive equation in the estimation of RMR in Chilean women with excess body fat, allowing a more accurate calculation of energy requirements, and facilitating the achievement of the objectives proposed by dietary prescription and nutritional therapy when indirect calorimetry equipment is not available. Therefore, the objective of the present study was to compare RMR measured by IC compared with RMR estimated by four predictive equations: FAO/WHO/UNU (1985), FAO/WHO/UNU (2004), Harris–Benedict, and Mifflin–St Jeor in young Chilean women with excess body fat.This was an analytical cross-sectional study.The sample consisted of 41 young adult Chilean women 18 to 28 years of age with overnutrition. The participants met the following inclusion criteria: without hypermetabolic pathology, no anemia, stable body weight (±10%) in the last 3 months, without medication consumption that modified RMR prior to the measurement, no pathological history, regular menstrual cycles, and not pregnant or breastfeeding.The present study was reviewed and approved by the Ethics and Biosecurity Committee of the Universidad del Bío-Bío and all the participants provided informed consent. The procedures were according to the ethical norms of the Declaration of Helsinki and the Council for International Organizations of Medical Sciences (CIOMS).To control the effect of the menstrual cycle on body composition and resting metabolic rate (RMR), all measurements were taken by the same evaluator between days 6 and 13 of the follicular phase of the menstrual cycle; this period was obtained from the analysis of each participant’s menstrual cycle . The antBody composition was measured by using bioelectrical impedance analysis  with BodThe nutritional status was diagnosed according to the percentage of body fat; body fat cutoff points were considered normal (20% to 30%), overweight (31% to 33%), and obese (>33%) .2 and VCO2 measurements, indirect calorimetry uses the Weir equation which relates RMR to oxygen consumption and carbon dioxide production. The equipment has a CO2 analyzer  and also a sensor for O2 detection .The indirect calorimetry method was applied (RMR IC) with the VMAX 29 N equipment , which belongs to the Energy Metabolism Unit of the Universidad del Bío-Bío. To estimate RMR from VO2 concentration < 3%. Prior to RMR measurement, the flow sensor was calibrated with a 3 L syringe, while the gas analyzers were calibrated with standardized gases (16% O2/4% CO2 and 26% O2) [The environment was controlled to ensure thermo-neutrality 20–24 °C)  and a CO 26% O2) . Each pa 26% O2) ,24. The  °C  and O2 (mL/min) [Test validity was ratified by the respiratory quotient value, which should show a normal physiological range from 0.7 to 1.0 . It shou(mL/min) .The results of the RMR IC were compared with the estimated RMR using the predictive equations of the FAO/WHO/UNU (1985), FAO/WHO/UNU (2004), Harris–Benedict, and Mifflin–St Jeor based on the actual weight of the participants see . When RMThe existence of adequacy, overestimation, and underestimation of the predictive equation was defined after calculating the percentage difference between RMR and RMR IC as expressed in Equation (3).Adequacy was understood to mean that the percentage difference between the estimated RMR and the RMR IC was within ±10%; that is, the result was adequate between 90% and 110%, and showed underestimation when it was <90% and overestimation when it was >110% ,29,30,31The normal distribution was verified by the Shapiro–Wilk test, and the variables were described by the median and percentiles. The Mann–Whitney and Kruskal–Wallis tests were used for comparison. We analyzed the concordance between the RMR predictive and the RMR IC according to the Bland–Altman method, the intraclass correlation coefficient (ICC), and coefficient of variation (CV). The information was processed with the STATA 16.0 software at a significance level of α < 0.05.The sample consisted of 41 young women from 18 to 28 years of age, whose nutritional status was overweight or obesity. In women with overweight, the medians (P50) for the age, weight, height, fat mass (%), free-fat mass (%), BMI, waist circumference, waist/hip circumference ratio, and RMR IC values were 22 y, 66.0 kg, 1.59 m, 30.9%, 69.1%, and 1.183.0 calories/day, respectively .p < 0.05)  for the age, weight, height, fat mass (%), free-fat mass (%), BMI, waist circumference, waist/hip circumference ratio, and RMR IC values were 23.5 y, 67.5 kg, 1.58 m, 35.3%, 65.1%, and 1.192.0 calories/day, respectively. Women with overweight and obesity showed statistically significant differences in the fat mass (%) and free-fat mass (%) variables ( < 0.05) .p < 0.001). In the group of women with overweight, the FAO/WHO/UNU (1985), FAO/WHO/UNU (2004), Harris–Benedict, and Mifflin–St Jeor formulae overestimated the RMR IC by 283.2, 311.2, 292.7, and 203.0 calories/day, respectively  of them expended < 1116 calories/day and 75% (P75) < 1295 calories/day. The RMR estimated by the FAO/WHO/UNU (1985) equation showed a median of 1466.2 calories/day, and 25% of subjects obtained values < 1392.7 calories/day and 75% < 1504.4 calories/day. When using the FAO/WHO/UNU (2004) equation, the RMR median was 1494.2 calories/day, and 25% of the subjects had an RMR < 1427.5 calories/day and 75% < 1760.9 calories/day. The Harris–Benedict equation showed a median of 1475.7 calories/day, and 25% of the women showed values < 1434.6 calories/day and 75% < 1500.7 calories/day. When applying the Mifflin–St Jeor equation, a median of 1386.0 calories/day was obtained, and 25% of the subjects showed values < 1340.7 calories/day and 75% < 1439.8 calories/day. There were statistically significant differences between the values obtained by the predictive equations and RMR IC (p < 0.001). In the group of women with obesity, the FAO/WHO/UNU (1985), FAO/WHO/UNU (2004), Harris–Benedict, Harris–Benedict adjusted weight (0.25), and Mifflin–St Jeor predictive equations overestimated the RMR IC by 296.7, 413.8, 280.0, 176.6, and 176.6 calories/day, respectively. Additionally, the Harris–Benedict adjusted weight (0.5) equation underestimated the RMR IC by 254.7 calories/day  equation, the median was 1488.2 calories/day, and 25% of the subjects showed RMR < 1392.7 calories/day and 75% < 1605.8 calories/day. The FAO/WHO/UNU (2004) equation results showed a median of 1605.3 calories/day, and 25% of the women obtained values < 1477.9 calories/day and 75% < 1790.4 calories/day. The median using the Harris–Benedict equation was 1471.5 calories/day, and 25% of the subjects had an RMR < 1420.7 calories/day and 75% < 1563.9 calories/day. The Harris–Benedict adjusted weight (0.25) equation showed a median of 1368.1 calories/day, and 25% of the women obtained values < 1336.8 calories/day and 75% < 1420.8 calories/day. The Harris–Benedict adjusted weight (0.5) equation showed a median of 936.8 calories/day, and 25% of the subjects obtained an RMR < 920.0 calories/day and 75% < 1378.3 calories/day. The estimation by the Mifflin–St Jeor formula showed a median of 1368.1 calories/day, and 25% of the subjects had values < 1307.1 calories/day and 75% < 1480.0 calories/day. There was a statistically significant difference between the values estimated by the predictive equations and the RMR IC  in 30.4% of the women; however, it overestimated the RMR IC in 69.5%. The Harris–Benedict equation showed a relevant overestimation in 86.9% of the participants .In the group of women with obesity, the Mifflin–St Jeor predictive equation provided the best adequacy (90% to 110%) in 55.5% of the women; however, it overestimated the RMR IC in 44.4%. The Harris–Benedict, FAO/WHO/UNU (1985), and FAO/WHO/UNU (2004) equations showed higher overestimation by 77.7%, 83.3%, and 88.8%, respectively. Finally, the Harris–Benedict adjusted weight (0.5) equation underestimated the RMR IC in 66.7% of the women .It is common in the nutrition consultation to estimate the RMR by predictive equations and then determine the total energy requirement using the factorial method . HoweverStudies have shown that predictive equations can overestimate or underestimate the RMR ,34, leadp = 0.001). The FAO/WHO/UNU 2004 equation showed the highest overestimation of 311.2 calories, while the Mifflin–St Jeor equation showed the lowest overestimation of 203.0 calories; these values are similar to those reported in other studies [The RMR IC median was similar between women with overweight and obesity p = 0.429) with 1183 calories/day and 1192 calories/day, respectively. In women with overweight, the FAO/WHO/UNU (1985), FAO/WHO/UNU (2004), Harris–Benedict, and Mifflin–St Jeor predictive equations overestimated (>110%) the RMR IC ( with 118 studies . For theThe overestimation of RMR IC obtained by the FAO/WHO/UNU (1985) equation has been reported in other studies ,38,39. TThe FAO/WHO/UNU (1985) and Harris–Benedict predictive equations overestimated RMR IC in subjects with overnutrition; this concurs with findings reported by Carrasco et al. in a study conducted with Chilean women with obesity . It also2; unfortunately, the ethnic composition of the subjects was not reported [The Mifflin–St Jeor equation showed the lowest overestimation of RMR in both women with overweight and obesity, so it is recommended as the most reliable, especially in subjects with obesity. This is consistent with what has been reported in other studies ,43,44. Treported . The Mifreported ,45. Howereported ,37,44. AIn patients with obesity, it is not clear which weight to use to estimate RMR by predictive equations, whether actual, ideal, or adjusted weight, despite the recommendation to use actual weight . To reduAny excess energy intake is stored in the body, and a positive energy balance between 6600 and 8000 calories produces a 1 kg gain in body weight . Given tOne of the strengths of the present study was that it carefully controlled the effect of several potentially important misleading factors when measuring RMR IC. Examples include taking the measurement during the follicular phase of the women’s menstrual cycle, absence of relevant medical conditions, and avoiding possible thermogenetic effects of food, caffeine, and nicotine.Given the high prevalence of overweight and obesity in Chilean women, there is concern that the estimation of RMR by predictive equations in clinical settings is inaccurate and exceeds the real energy needs of the individuals to whom the estimation is applied. If it is not feasible to measure the RMR by IC, the Mifflin–St Jeor equation could be an option for the group of overweight women or those with obesity because it overestimated less and has better adequacy. However, it is also very important to clarify that this method is not free of inaccuracies . FinallyIn conclusion, the analyzed predictive equations overestimated the resting metabolic rate by indirect calorimetry (RMR IC) in a group of young Chilean women with overweight or obesity (30.6% to 36% fat mass). However, the estimation by means of the Mifflin–St Jeor equation using real weight could be the recommended option among the equations analyzed both for sport nutrition or nutritional therapy, as it presents the lowest overestimation and the best adequacy, even though it is not exempt from inaccuracy. The Harris–Benedict equation with adjusted weight (0.50) should not be recommended, which showed a relevant and worrisome underestimation.


Oxygen metabolism in the mitochondria is essential for biological activity, and reactive oxygen species (ROS) are produced simultaneously in the cell. Once an imbalance between ROS production and degradation (oxidative stress) occurs, cells are damaged. Sensory organs, especially those for hearing, are constantly exposed during daily life. Therefore, almost all mammalian species are liable to hearing loss depending on their environment. In the auditory pathway, hair cells, spiral ganglion cells, and the stria vascularis, where mitochondria are abundant, are the main targets of ROS. Excessive generation of ROS in auditory sensory organs is widely known to cause sensorineural hearing loss, and mitochondria-targeted antioxidants are candidates for treatment. This review focuses on the relationship between acquired hearing loss and antioxidant use to provide an overview of novel antioxidants, namely medicines, supplemental nutrients, and natural foods, based on clinical, animal, and cultured-cell studies. Science, technology, and innovation provide us with treatments for diseases, life extension, and diversification of lifestyles. In otology, they have uncovered the mechanisms of sensorineural hearing loss and improved activities of daily living for patients who experience sensorineural hearing loss. Some medications, aging, and living environments with noise exposure cause drug-induced, age-related, and noise-induced hearing loss, respectively. The causes of these acquired hearing losses are fundamentally different. However, cellular damage due to oxidative stress in these pathologies is a common phenomenon at a molecular level. Therefore, understanding the mechanisms of oxidative stress can provide a basis for the treatment of acquired hearing loss.Eukaryotes have evolved to utilize the energy generated during oxygen metabolism by incorporating mitochondria. In other words, reactive oxygen species (ROS) were inevitably produced in the process of oxygen metabolism. ROS are essential for biological activity and vice versa. The main physiological functions of ROS are of cellular transmitters ,2 and siCell death in auditory sensory organs is associated with sensorineural hearing loss (SNHL) . In the The aim of this review was to describe the relationship between acquired hearing loss and antioxidants. Based on clinical, animal, and cultured-cell studies, we provide updated information on novel antioxidants including medicines, supplement nutrients, and natural foods in addition to details about vitamins, especially the relationship between vitamins in neurodegenerative diseases and inner ear disorders. First, we focus on auditory processing and the pathology of hearing loss. Second, we describe the role of oxidative stress in mitochondrial function. Finally, we provide a clear overview of antioxidants used in the treatment of acquired inner ear disorders. Sound travels via the outer and middle ears and is encoded in the cochlea of the inner ear A. The fu2+ channels, which release the neurotransmitter glutamate from synaptic vesicles, resulting in the transmission of auditory signals to afferent nerve fibers [Above the basilar membrane, the organ of Corti is composed of epithelial cells C. The ore fibers . Converse fibers . In geneHearing loss is categorized as conductive, sensorineural, or mixed. Conductive hearing loss is caused by the interruption of sound waves from the external auditory canal to the middle ear cavity A. The caDrug-induced hearing loss is irreversible and is generally caused by the ingestion of ototoxic drugs. The primary mechanism underlying hearing loss is injury to hair cells . Drugs mPlatinum-based anticancer drugs are used to treat squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinomas of the head and neck, lungs, and bladder . PlatinuThe induction of ROS production by cisplatin results in hearing loss. The cochlear sensory epithelium and ROS-producing enzymes NADPH oxidase 3 (NOX3) ,52 and xAge-related hearing loss is defined as the progressive SNHL associated with aging. Many factors, including genetic, environmental, and medical, have been implicated as causes, although the exact mechanism is unknown ,60. HistSOD1 knockout mice develop premature age-related hearing loss due to hair cell loss . Mouse mNoise-induced hearing loss is defined as partially irreversible hearing loss associated with intense sound exposure. The main pathogenesis is mechanical damage ,82,83, mROS is a general term for substances in which oxygen is transformed into more reactive compounds. The four most common types of radicals are hydroxyl radicals, superoxide anions, hydrogen peroxide, and singlet oxygen. Most of these ROS are produced in the mitochondria ,98. ROS Mitochondrial DNA mutations are associated with both syndromic and non-syndromic hearing losses. Syndromic hearing loss is associated with systemic neuromuscular diseases such as mitochondrial disease with stroke (MELAS), mitochondrial encephalomyopathy, chronic progressive exophthalmoplegia, lactic acidosis, and mitochondrial encephalomyopathy with ragged red fibers ,119,120.Antioxidants are defined as substances that inhibit ROS generation and control oxidative stress. Antioxidants are broadly classified into endogenous antioxidant enzymes produced in vivo and exogenous antioxidants that are supplied from outside the body. Exogenous antioxidants consist of water- and lipid-soluble components. Bipolar antioxidants, such as alpha-lipoic acid, act as antioxidants and restore the antioxidant effects of glutathione, vitamin A, vitamin C, and vitamin E. 2O2 by SOD. H2O2 is subsequently decomposed into water and oxygen by GPX and catalase, thereby eliminating ROS. N-acetyl-L-cysteine (NAC), a precursor of glutathione, also exhibits antioxidant properties [2O2-induced oxidative stress but also inhibits pyruvate kinase M2 (PKM2). Silencing PKM2 diverts the above-mentioned glucose metabolic pathway [phox protein is a subunit of NOX and is an essential component for the stabilization of NOX. NOX2, 3, and 4 are expressed in the organ of Corti, stria vascularis, and spiral ganglion cells in mice [−/− mice are vulnerable to noise exposure, and in SIRT3−/− mice administered with nicotinamide riboside, an NAD precursor, hearing levels are not protected against noise exposure [Endogenous antioxidant enzymes include SOD, glutathione peroxidase (GPX), and catalase . The supoperties . Ebselenoperties . Excessioperties ,143,144.operties ,146. Act pathway . In the  pathway . NADPH o in mice . Sirtuinexposure . Known water-soluble antioxidants include methionine, vitamin C, carnitine, riboflavin (vitamin B2), niacin, folic acid, polyphenols, and catechins.Methionine, an essential amino acid, lowers blood cholesterol levels and removes ROS . RiboflaLipid-soluble antioxidants inhibit lipid oxidation reactions in the cell membranes. Β-carotene, vitamin E, astaxanthin, and coenzyme q10 (CoQ10) are widely known and used as supplements. Other potential antioxidants include carotenoids such as α-carotene, γ-carotene, lycopene, and xanthophylls, which are lipid-soluble pigments found in plant collagen. The pro-vitamin A activity of β-carotene removes the singlet oxygen. Vitamin E contributes to the stability of biological membranes. Astaxanthin removes singlet oxygen and is a pro-oxidant; CoQ10 removes lipid radicals in cellular and mitochondrial membranes and inhibits oxidative damage . CoQ10 aGinkgo biloba and alpha-lipoic acid. Ginkgo biloba (EGB761) has antioxidant properties and acts as a scavenger of peroxyl radicals [Antioxidants with both water- and fat-soluble properties include radicals . In factradicals . Alpha-lradicals . Oxidative stress plays an important role in SNHL. Accumulation of ROS is considered to be the main cause of acquired hearing loss. The protective effects of antioxidants have been investigated, and it is postulated that antioxidants are effective in many cases of SNHL of an unknown etiology. Edaravone , a radicBak expression in the spiral ganglion cells and outer hair cells and prevents Bak-dependent apoptosis in the cochlea of C57BL6/J mice [phox deficient A/J mice (nmf333), outer hair cells, synaptic ribbons, and spiral ganglion cells were restored, indicating that NOX inhibitors are candidates for the treatment of age-related hearing loss [Various antioxidants have been investigated for age-related hearing loss, and their protective effects have been confirmed in animal experiments. However, the role of antioxidants in human studies remains controversial. Vitamin C has different effects on humans and animals. CoQ10 significantly prevented age-related changes in both animal experiments and human studies. In fact, administration of alpha lipoic acid and/or CoQ10 inhibits 6/J mice . In a cl6/J mice . Sixty p6/J mice . A/J micing loss . Animal Nqo1, Ho-2, Gclc, Gclm, and Txnrd1 [GSH is a strong antioxidant that prevents ROS production. Pigmented guinea pigs treated with GSH preserved their hearing after noise exposure . ABR thresholds at 2, 4, 8, 12, 16, and 20 kHz of GSH-treated animals were improved, and the results were consistent with those of histological examination on cytocochleogram ,173. i. d Txnrd1 . In recent years, natural dietetic antioxidants have drawn attention, owing to their potential effects on human health. Large-scale human prospective cohort studies have been performed to confirm the effects of antioxidants for neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease.Parkinson’s disease is distinguished by a significant loss of dopaminergic neurons in the substantia nigra pars compacta as well as the appearance of insoluble protein inclusions known as Lewy bodies. The main pathologies of Alzheimer’s disease are the formation of amyloid-β plaques surrounded by neurons and deposition of hyperphosphorylated tau protein inside the neurons. A meta-analysis of human studies conducted to determine the effects of vitamin C, E, and β-carotene suggested that dietary intake of vitamin E protects against Parkinson’s disease, but not vitamin C and β-carotene intake . VitaminAntioxidants are expected treatments for SNHL because of analogies of an anatomical structure and pathology between inner ear disorder and neurodegenerative disorders. Dopaminergic neurons, the main target of Parkinson’s disease, innervate the axon terminal of type I spiral ganglion neurons and the axon terminal of the medial olivocochlear nerve . AccumulThere are many antioxidants in natural foods, such as fermented papaya , ferment2O2-induced DNA damage and reduces H2O2-induced p38 phosphorylation, leading to reduced apoptosis. In an in vitro study, FPP reduced amyloid-β precursor protein levels by reducing oxidative stress [3, and E), and minerals [1, B2, and C), and β-carotene [Fermentation is a traditional method of food preparation that extends the shelf life and enhances the flavor of food matrices, such as fruits and milk. Recent studies suggest that fermented foods are important components of the human diet owing to their high concentration of health-promoting chemicals, as fermented foods contain a higher fiber content, amino acids, essential fatty acids, vitamins, and minerals . Fermente stress . The effe stress . The maiminerals . In a clminerals . Hibiscucarotene . The antcarotene  and in vcarotene  experimecarotene . The biocarotene . In vivocarotene . Alternacarotene . However, there are no reports on the relationship between acquired inner ear disorders and antioxidants such as fermented milk products, extract of hibiscus, and rosemary essential oil. In the following section, we will describe the therapeutic potential of green tea and brown seaweed for acquired inner ear disorders.The antioxidant effects of green tea have been extensively investigated. Green tea contains various components with antioxidant activity such as polyphenols, including catechins, minerals , and vitamins . In vitro and animal studies have revealed the effects of polyphenols in green tea against hearing loss. Noise-exposed guinea pigs treated with polyphenol developed hearing loss, but the threshold of ABR and the expression levels of caspase-9 and caspase-3 proteins were low and hair cell loss was significantly decreased compared with those of the non-treated group . Epigall1, B12, C, D, E, riboflavin, niacin, pantothenic acid, and folic acid). Hydrogen peroxide scavenging activity in brown seaweed extracts was higher than that of the commercial oxidants such as vitamin E, butylated hydroxyanisol, and butylated hydroxytoluene in an in vitro study [Brown seaweed contains polysaccharides, minerals , polyunsaturated fatty acids, and vitamins  was performed to identify the most relevant studies reported in English. The following query was used: ((antioxidant OR antioxidants) AND ). We screened all 34 records and removed 28 studies that were not relevant to the subject matter. Three studies were completed in 2017, 2014, and 2010. All three reports are available on the website, and the last study was only published in print [To understand the effects of antioxidants on SNHL, we searched a database of clinical studies registered at the National Institutes of Health until 3 June 2022. A query-based Clinical Trials search  for cancer patients undergoing treatment with cisplatin, and the administration of alpha-lipoic acid continued until 3 months after the final treatment. The third used NAC (1200 mg/day) for noise-exposed workers, and the supplement was administered for 2 weeks . The thrMedications, supplemental nutrients, and natural foods have a potential role in the prevention/therapy of hearing loss . IdeallyThe effects of antioxidants on acquired inner ear disorders are poorly understood because almost all the reports discussed here are animal studies. Further clinical research is required to clarify the mechanism underlying acquired inner ear disorders and the effects of antioxidants on hearing loss.


Cytoreductive surgery for advanced ovarian cancer commonly involves bowel resection. Although UK gynaecological oncologists are trained in bowel surgery, the degree to which they perform bowel surgery independently varies nationally. A recent joint policy statement from the British Gynaecological Cancer Society (BGCS) emphasises the need for formalised colorectal support. An anonymous, online survey was emailed to BGCS members to assess the status of multidisciplinary working between UK gynaecological oncology and colorectal/general surgical teams. A total of 46 members responded (8.2% response rate). There was a large variety in the involvement of colorectal/general surgical teams in preoperative planning. A total of 13% of respondents had no formalised agreement for intraoperative support, 72.1% of respondents independently performed rectal peritoneal stripping and 60.5% independently performed small bowel resection. This was reduced to 27.9% for right hemicolectomy with primary anastomosis and 16.3% for left hemicolectomy with primary anastomosis. Respondents often involved colorectal support for post-operative complications. The majority of UK gynaecological oncologists involve colorectal/general surgical teams in bowel procedures, more commonly for large bowel procedures compared to small bowel and for left colon compared to right colon procedures. A total of 16.3% of respondents independently performed all surveyed bowel procedures. Future research should examine training and experience within these groups to address this disparity. Gynaecological Oncology was first defined as a subspeciality of obstetrics and gynaecology in 1969 by the American Board of Obstetrics and Gynaecology, leading to the development of a certified post-residency training programme [In 1982, the UK Royal College of Obstetricians and Gynaecologists (RCOG) also recognised Gynaecological Oncology as a subspecialty and highlighted the need for links between the subspecialty and general and urological surgeons [Since then, the concept of a multidisciplinary approach to gynaecological oncology surgery has become essential. Systematic review demonstrates patients with advanced ovarian cancer benefit from treatment in dedicated gynaecology oncological centres, with subspecialist and multidisciplinary input ,4.Surgical treatment of advanced ovarian cancer centres around cytoreductive surgery, which requires appropriate training in radical pelvic surgery, including colorectal and urological procedures. However, surgical practice varies internationally, as do survival outcomes . CompariTo standardise surgical training, the European Society of Gynaecological Oncology (ESGO) has set out a curriculum for trainees . FurtherThe policy statement highlights the importance of involving colorectal surgeons prior to surgery if their input is anticipated. The statement also recognises that the degree to which colorectal surgeons will be involved in bowel surgery will vary depending on the experience of the gynaecological oncologist and surgical centre. Nevertheless, protocols for the postoperative management of these patients should be agreed between both gynaecological oncology and colorectal/UGI surgical departments. The statement consequently highlights the importance of appropriate colorectal training for gynaecological oncologists.This study consequently sets out to assess the current status of multidisciplinary work between gynaecological oncology and colorectal/general surgical teams in the UK.An online survey was emailed to all 569 members of the British Gynaecological Cancer Society (BGCS) in December 2021 using SurveyMonkey, with a reminder email sent four weeks later. A preliminary scoping survey was emailed one year prior, with 22 responses, helping to determine which themes to explore in more depth.Survey data were collected anonymously, with 28 multiple-response questions and opportunities to provide open responses. The survey was divided into two sections. The first section ascertained the working habits, training and access to colorectal surgeons in the pre- and peri-operative periods.The second section explored the role of colorectal/general surgical support in common bowel procedures performed during cytoreductive surgery and their input with surgical complications and post-operative management. The survey questions and answer options are detailed in A core outcome set (COS) was not used, as there are none in development regarding ovarian cancer at present.Data were processed and analysed in excel, with descriptive statistics detailed below. Ethical approval was not required for this survey.A total of 46 surgeons responded (8.2% response rate) to the first section of the survey, with 43 (7.7%) of these also completing the second section.A total of 93.5% of respondents described themselves as a consultant gynaecological oncologist, with the remaining respondents including fellows and trainees. A total of 87.0% of respondents were subspecialists trained in gynae-oncology with GMC accreditation. One respondent was not GMC-accredited but had completed an advanced training skills module (ATSM). A total of 10.9% were not subspecialists, again including fellows and trainees, as well as gynaecologists prior to starting subspecialty training and a medical oncologist.A total of 95.6% of respondents worked in a tertiary centre, and 87.0% had formal training in exenterative surgery, including bowel resection with anastomosis or stoma formation.A total of 91.3% had access to colorectal/general surgical support onsite, with the remaining 8.7% having access on a remote basis.Ovarian cytoreduction surgery made up over 40% of operating cases for 41.3% of the surveyed respondents.Regarding primary surgical debulking (PSD) of advanced ovarian cancer (stage 3 and 4), 54.4% of respondents commented that more than half of patients would receive PSD rather than neoadjuvant chemotherapy. Concerning advanced ovarian cancer surgery, 17.4% had a dedicated colorectal surgeon routinely attending cytoreductive surgery, 69.6% had colorectal support available on a standby basis when required intraoperatively, and 13.0% relied on the on-call team to attend if colorectal support was required intraoperatively, with no formalised agreement.With regard to the initial MDT pre-operative assessment, 26.1% had formal colorectal/general surgery input, 37.0% had such colorectal/general surgery available for advice on preoperative planning, and 37% had no input from such teams in preoperative planning of cytoreductive surgery patients.Within Respondents answered questions on different colorectal procedures; the results are detailed in Respondents were most confident when independently performing mesenteric/serosal disease (74.4%), rectal peritoneal stripping (72.1%), and small bowel resection with ileostomy (60.5%) or primary anastomosis (60.5%). In contrast, respondents were less likely to undertake procedures of the large bowel. Colorectal/general surgical teams would be more likely to undertake left hemicolectomy with recto-sigmoid resection and primary anastomosis (53.5%), transverse colectomy with primary anastomosis (48.9%) right hemicolectomy with primary anastomosis (48.8%), and sigmoid colectomy with primary anastomosis and de-functioning ileostomy (48.8%). Across large bowel procedures, respondents were less likely to perform procedures independently where such procedures involved primary anastomosis, compared to stoma formation.Main Findings:This study demonstrates national discrepancies in colorectal/general surgical support for patients with advanced ovarian cancer. A total of 13% of respondents had no formalised agreement for intraoperative support from colorectal/general surgical teams, instead relying on on-call teams. This survey also shows that gynaecological oncology surgeons most often undertake bowel procedures with colorectal support. However, particularly for bowel resection with stoma formation or anastomosis, a large proportion of procedures are performed purely by colorectal teams.Although nearly 90% of respondents would always or often involve colorectal support for post-operative complications, over two thirds of respondents rarely seek support for post-operative instructions such as establishment of oral intake. This may reflect standardised post-operative protocols for aspects such as establishing oral intake. In fact, open responses highlighted the role of joint postoperative ward rounds with colorectal colleagues.Strengths and Limitations:One weakness of this study is a low response rate. This may be due to the survey email being missed by recipients. The length of the survey, at 28 questions, may have also deterred recipients from completing it. Three of the 46 respondents only completed the first section of the survey. Furthermore, it is unclear if the survey population represents surgeons that are more or less experienced in bowel procedures.Nevertheless, the survey length does facilitate an exploration of colorectal support in the pre-, peri- and post-operative stages of cytoreductive surgery, alongside a large range of bowel procedures commonly performed during cytoreductive surgery.Interpretation:The findings of this study contradict the BGCS joint policy statement that colorectal colleagues should only be called on in emergency situations in exceptional circumstances . SimilarThe ESGO Gynaecology Oncology curriculum expects trainees or fellows to undertake a minimum of 20 cytoreductive surgeons as first surgeon. These should include either bowel resection, upper abdominal procedures or bulky lymph node resection . The UK The surgical approach to bowel resection also differs for cytoreductive surgery compared to bowel resection for a primary bowel cancer. The aim of debulking is to remove visible disease to improve the effects of chemotherapy agents . In compIn a 2018 survey of Spanish trainees in the European Network of Young Gynaecological Oncology (ENGYO), 78.4% of respondents identified bowel surgery as an area of training they felt was most required . For smaOur findings may also relate to opinions on cytoreductive surgery within gynaecology oncology in the UK. A survey of gynaecological oncologists in the UK, Norway, Australia, Denmark and Canada showed a significant difference in their opinions on ‘ultra-radical’ surgery for patients with advanced ovarian cancer . All AusThe BGCS policy statement does recommend that post-operative management follows locally agreed protocols, with the management of complications agreed between gynaecological oncology and colorectal/UGI teams . This suColorectal and general surgical colleagues are commonly involved in managing post-operative complications of advanced ovarian cancer. However, there is variation in the involvement of these teams in pre-operative planning. Despite nearly all survey respondents working in tertiary care centres, on-site colorectal support is not always available and, in some instances, there is no formal agreement regarding intraoperative colorectal support. The findings of this study, therefore, suggest that the governance frameworks set out in BGCS’ joint policy statement are not being fully implemented. While some centres perform bowel procedures almost completely independently, others are much more reliant on colorectal or general surgical teams.For centres where gynaecological oncologists are performing most bowel procedures independently, future research should examine useful lessons that can be implemented elsewhere, for example, more training in large bowel surgery. It would be useful to conduct qualitative research to build on this study. Through semi-structured interviews, it may be easier to explore the barriers that exist to multidisciplinary working within advanced ovarian cancer and suggest potential solutions to addressing the variation in colorectal/general surgical support.As the joint policy statement suggests a reciprocal relationship regarding gynaecological support in colorectal procedures, it would also be useful to survey colorectal consultants and ascertain how gynaecological colleagues support them in the pre-, peri- and post-operative periods. There is a well-established national bowel cancer audit; however, no similar system exists in gynaecological oncology . The joi


Hearing represents the main source for acquisition of language and speaking skills in childhood. In the first months of life, the hearing impaired child is deprived of sound stimulation in the most important period of development, and consequently, might present emotional, social and linguistic disorders. Therefore, it is of utmost relevance to learn about the main etiological factors that cause the auditory damage to trace a reliable nosological profile, and to take the appropriate measures to prevent and guide the family on the repercussions of hearing impairment in childhood.To characterize the etiology profile of hearing impairment in a reference center for hearing impaired children and adolescents.We performed interviews, speech and hearing screening and analyses of medical charts of 87 hearing impaired children that were part of Associação de Pais e Amigos dos Deficientes Auditivos do Estado da Bahia (APADA-BA), trying to define etiology, gender distribution, age at diagnosis, level of hearing loss, age at hearing aid fitting, and rehabilitation.Among the 87 children and adolescents who had undergone speech and hearing screening, we select a sample of 53 subjects, whose parents had come for three sessions of anamnesis and assessment. The main responsible etiological factor for hearing loss in the evaluated population was maternal rubella, amounting to 32% of the cases of deafness, followed by pyogenic meningitis with 20%, idiopathic cause with 15%, prematurity with 9%, heredity (deaf father or mother) and neonatal jaundice, which also presented 6% incidence; chronic otitis media represented 4%, use of misoprostol in the gestation, measles, ototoxicity and mumps, each factor with 2%.The present study demonstrated the heterogeneity of factors that cause hearing impairment, and the two main causes (rubella and pyogenic meningitis) still present high incidence in the studied population. We believe that preventive measures must be taken, especially in the prophylaxis of maternal rubella and extended vaccination of neonates and infants against bacterial meningitis. The ear is an organ that enables human beings to exert one of the noblest superior functions: communication. It is through language that we have been able to organize the universe, to understand the world around us, to comprehend our fellow human beings, to convey and examine thoughts and feelings of others, to interact with the environment and to acquire knowledgeLanguage is a highly complex process, as it relates to the elaboration and symbolization of human thought to allow communication between men. The ability to understand oral language must be considered one of the most important measurable aspects of human auditory functionIn hearing impaired children, language acquisition and development process can be put in harm's way, should diagnosis and intervention not be done in a timely manner.Research has also indicated the existence of a critical period that occurs within the first years of a child's life for speech acquisition. Lack of proper auditory stimulation in childhood may preclude the complete development and maturation of central auditory pathwaysAccording to the WHO, 42 million people above the age of three bear some sort of moderate to profound hearing loss. Over 4% of the children considered to be at high risk are diagnosed with moderate to profound hearing lossThis paper aims at characterizing the etiological profile of hearing impairment at a reference center for the treatment of hearing challenged children and adolescents, so as to enable future prevention and care measures.The identification of the main etiologic factors surrounding infantile deafness is an important diagnostic tool to allow the proper implementation of public health procedures and, consequently, of effective prevention measures and guidance to families in regards of hearing impairment.The APADA - BA  is a nonprofit organization that provides specialized support to deaf children and adolescents by means of psychopedagogy, speech and hearing therapy, psychology, and employment bureau services. It also counts on the support of a public secondary school that works within APADA premises where teachers, aside from the traditional curricula, teach Brazilian Sign Language (LIBRAS) to students.A case series cross-sectional study was carried out. All selected children and adolescents were interviewed three times . The adopted screening protocol comprised interviews and speech and hearing evaluations, in which the main etiologic factors were analyzed by assessing the subjects’ prenatal history, their neuropsychomotor development, and test results brought in by their families and those already available from the subjects’ charts.The items analyzed were distribution by gender, age of diagnosis, hearing loss severity, age of hearing aids introduction, and speech and hearing rehabilitation sessions attendance.The project was submitted to the Research Ethics Committee of the Federal University of Bahia, at the Medical School Graduate Department, and was granted permit # 89/ 2004, knowledge area code 4.07, level D, Group III.Fifty-three subjects were chosen from the original sample of eighty-seven who underwent speech and hearing screening. Their parents attended all three interview and evaluation sessions. The main etiologic factor responsible for hearing impairment in the assessed population was mother's rubella, accounting for 32% of deafness cases, followed by pyogenic meningitis with 20%, idiopathic reasons with 15%, premature birth with 9%, inheritance (deaf father or mother) and neonatal jaundice with 6% each; chronic otitis media accounted for 4%, use of misoprostol during pregnancy, measles, ototoxicity, and mumps were also present, each with 2% .Chart 1DThirty-one (58%) of the 53 subjects were males and 22 (42%) were females. Ages varied between 4 and 18 years. In the speech and hearing evaluation interview the main causes for hearing loss onset on the prenatal, perinatal, and postnatal periods were addressed, the age of diagnosis, the type of hearing aid device used, and the subjects’ ability to use either oral language or the Brazilian Sign Language. Results are described below .Chart 2HPrenatal factors were identified in 43 of the 53 subjects in the sample (81%). Age of diagnosis < 2 years - 34%, between 2 and 3 years - 40%, and above 3 years of age - 26%. The hearing aid device found predominantly was AASI (58%), while 42% of the children never wore or discontinued the use of the device for various reasons , and had not worn it in over 6 months.The vast majority of the subjects used the Brazilian Sign Language as their main form of communication (62%), while only 38% used oral language as their principal means of communication.As for the type of hearing impairment, the entire sample presented sensorineural hearing impairment and 33 individuals (62%) presented audiometric configuration compatible to bilateral loss, while only 10 children (18%) had unilateral loss. Thirty subjects in the sample (56%) had profound loss, 25% of them had severe loss, while 19% presented moderate to severe loss. Chart 3TyAccording to Walch et al.Infantile development depends basically on two aspects: the child's individual characteristics – organic and emotional conditions and environmental characteristics – social and familial conditions; and learning opportunities. The global development – cognitive, linguistic, and emotional – is determined by the interaction between these various factorsInherited hearing impairment is considered to be of prenatal origin, and in this stage fetal infections play a role of paramount importance as causal factors. The main fetal infection to cause hearing impairment is rubella. However, with the introduction of immunization programs the incidence of this disease has decreased in developed countries in the last few decades. But rubella and other fetal infections are still quite prevalent in the Brazilian northeastern states, and should always be taken into consideration in the etiologic analysis of infantile congenital hearing lossLater in childhood, the biggest cause of hearing impairment is meningitis, a disease that may lead to profound hearing loss. About one out of every one thousand newborns present hearing loss, and two out of every one thousand children begin to experience deafness within the first three years of life. These facts by themselves justify audiologic investigation in children not only when they are born, but also throughout their first years of lifeThe current trend in regards to hearing impairment points to diagnosis, etiology, and treatment within the boundaries of pediatric otological and otoneurological diseases, apart from neonatal and infant screening tests aiming at early hearing rehabilitationOne of the biggest challenges in pediatric audiology lies in the cases of hearing losses of unknown etiology in childhood. Parents must be thoroughly interviewed. Information coupled with data from audiologic tests can lead to the development of an etiologic diagnosis of the patient's hearing impairment. It is also recommended to include non-audiologic tests such as serology, imaging, ophthalmologic examination, and genetic evaluation. A broad interdisciplinary approach may offer valuable insight into uncovering unknown etiologiesChanges in the prevalence rates of infantile hearing impairment have been observed throughout the years. And many and different are the epidemiological aspects to be considered from country to country and even inside one same nation. In most developed countries the pediatric health care systems monitor children's development and offer follow-up and rehabilitation programsBroad educational programs must be implemented to advise health care workers of the harm brought about by hearing impairment. The development of informational material can play a key role in the early detection of hearing impairmentThe etiologic identification done at the APADA population unveils many of the main factors at play in hearing impairment. It also calls for further studies in other centers so that a nosological profile of deafness can be properly outlined and input is provided to public health policy makers. The occurrence of diseases such as measles during pregnancy, and infectious contagious diseases such as meningitis, must be minimized so as to mitigate the impact of infantile hearing impairment.