Age-Related Hearing Loss (ARHL) is the most widespread sensory disorder in the elderly. Poor audiological support within retirement homes is one of the fundamental issues impacting the Quality of Life (QoL).The objectives of this study were to: (1) Identify the presence of hearing impairment through a hearing screening test battery in a sample of elderly participants residing in three retirement homes. (2) Determine the psychological, communication-related and social impact of the hearing impairment on the QoL in a sample of elderly participants residing in retirement homes.A prospective cross-sectional research design with quantitative methods of data analysis was used to obtain data from 70 elderly participants . Ten of them used hearing aids. Hearing screening was conducted using otoscopy, tympanometry and air conduction screening (500 Hz–4 kHz). The World Health Organization Quality of Life (WHOQoL) questionnaire was adapted and utilised for the present study.n = 16) of the participants felt depressed, worried and anxious because of their hearing loss and 20% of participants felt unaccepted by their significant others as a result of their hearing impairment. Hearing difficulties were significantly associated with a reduced QoL (p = 0.045). Eight of the 10 participants who wore hearing aids reported an overall improvement in QoL since receiving and utilising their hearing aids and 20% (n = 2) of hearing aid users reported challenges with maintaining their hearing aids.Findings revealed that 77% of the sample obtained a refer result from the hearing screening protocol indicating a high presence of hearing impairment. Twenty-nine per cent (The findings of this study emphasised the need for an increased role for audiological services provided by audiologists within retirement homes, thereby contributing to an improved QoL. Hearing impairment, the most wide-spread sensory disorder in the elderly, is of growing concern  describes QoL as individuals’ perception of how their health, wellness, culture, living conditions and environment affect the psychological or emotional state, social relationships, independence, communication and personal beliefs. For the purposes of this paper, QoL will specifically refer to the psychological or emotional impact of hearing impairment on life as well as its impact on social relationships. Studies indicate that elderly individuals residing in retirement homes (both within a state and within the private context) have a greater prevalence of hearing loss and an associated reduction in QoL Chalise, . SalonenThe above perusal of literature confirms four important aspects. Firstly, there is a high prevalence of ARHL; secondly, this hearing impairment can lead to a reduced QoL, especially if there is poor hearing aid support. The role of the audiologist in improving QoL for the elderly with ARHL is understated in literature. Finally, literature also affirms that there is a paucity of studies within the South African context relating to hearing loss and associated QoL issues amongst the elderly.It is therefore worth investigating these issues within the SA context so that findings emerging from such studies may be assimilated into designing contextually relevant hearing screening programmes and evidence-based intervention for the elderly residing in retirement homes. The purpose of the study was therefore, to determine the presence of hearing impairment and its impact on QoL for the elderly residing within retirement home facilities.The objectives of the study were to: (1) Identify the presence of hearing impairment through a hearing screening test battery in a sample of elderly participants residing in three retirement homes. (2) Determine the psychological, communication and social impact of the hearing impairment on the QoL in a sample of elderly participants residing in retirement homes.The study employed a cross-sectional research design that aimed to investigate both the presence of hearing impairment through a hearing screening test battery as well as to determine the impact of hearing impairment on QoL through a questionnaire at one point in time in a sample of elderly participants residing in retirement homes.Several sites in Pretoria, including both government and private retirement homes, were invited to participate; however, the majority of participants were from private retirement homes with only one state retirement home providing permission.n = 70) of the estimated sample size was obtained.A total of five retirement homes, four classified as private retirement homes and one as a state facility, consented to participate, with a total population of 500 elderly individuals within these retirement homes. The minimum recommended sample size for the study was calculated to be 218 by applying a 5% margin of error, 95% confidence level and 50% response distribution. Because of time constraints, participant refusal and cognitive disorders, only 30% , Titan middle ear analyser and DPOAE screener and RS PRO RS-95 Sound Level Meter were calibrated and used for data collection. A questionnaire was utilised to understand the perceived impact of hearing loss on QoL The World Health Organization Quality of Life (WHOQoL) disability questionnaire consists of four domains: namely physical, psychological, social and environmental. The questions relating to social and psychological factors and communication were adapted from the WHOQoL disability questionnaire WHO, . AdditioA hearing screening test battery and administration of the questionnaire was conducted on 60 participants and 10 additional participants only completed the QoL questionnaire as they were already diagnosed with hearing impairment and wore a hearing aid.n = 60) without hearing aids. Otoscopy, pure tone audiometry (Pta), tympanometry and otoacoustic missions (OAEs) screening were conducted. Pure tone audiometry was conducted over the range of 500 Hz–4 kHz according to the protocol. The intensity level was set at 25 dBHL  as well as those already fitted with hearing aids (n = 10) completed the adapted WHOQoL questionnaire. Because of dexterity and visual problems, the researchers and nursing staff assisted participants in completing the questionnaire by reading out the questions. The researchers conversed in English and Tswana, and for participants that spoke Afrikaans only, the nursing staff were available to translate the questions. The questionnaire comprised simple and easy to follow questions. All of the questions were either yes or no or multiple-choice questions. Participants who used or were fitted with hearing aids previously (n = 10) were required to complete an additional section of the questionnaire (Section C), that explored hearing aid use. This section required the participants to mainly respond to yes or no questions and to state their primary challenges with hearing aid use if applicable.Participants who underwent hearing screening .The reliability and content validity of the questionnaire utilised in this study was ensured by using questions from a valid and reliable standardised questionnaire  to evaluate the reliability of the hearing screening test battery, (2) to test the reliability of the questionnaire. The researchers ensured that the hearing screening equipment was calibrated and therefore, reliable results were obtained. The screening test battery was conducted by researchers in an environment with low ambient noise to improve reliability. The participants were able to respond appropriately to the tonal stimuli, indicating that they understood the instructions. Feedback was given to the participants, referring the participants who failed the screening and obtained a refer result to an audiologist for a diagnostic assessment. Noise levels were noted to be a problem during the pilot study and impacted on the screening test. For the main study, a quiet room was identified, and noise level measurements were routinely taken to monitor noise levels.The participants needed to verbally respond ‘yes’ or ‘no’ to questions relating to the ease of use of the questionnaire. The questions related to the number of questions, language simplicity and ease of understanding (comprehension). All five participants reported no problems filling in the questionnaire; therefore, no changes were made to the questionnaire.Bias was likewise avoided through careful design of the data-collection tool; addressing the participants regarding the purpose of the study; the use of simple and accessible language; avoiding of double-barreled questions and testing data-collection tools through a pilot study . Furthermore, no participants were harmed or exposed to any risk and confidentiality was assured. Participants willingly provided informed consent and were free to withdraw at any stage. Participants with cognitive challenges were excluded from participation. Confidentiality and anonymity were maintained throughout the study as information derived from this study was not disclosed, and research codes replaced names. Questionnaires and hearing screening results were additionally stored in a locked cabinet and access to the research data was available only to the researchers, research supervisor and the statistician. All participants who obtained a refer result were appropriately referred. Researchers also used calibrated equipment and maintained measures to control infection at all times. Regarding beneficence, all participants received a pamphlet on ear care; participants screened or who required hearing aid support, were appropriately referred.The results are discussed in accordance with the objectives of the study.n = 64). The results obtained from the hearing screening test battery revealed that 23% (n = 14) of participants passed the screening and 77% (n = 46) of participants obtained a refer result. Of those participants that obtained a ‘refer’ result, 15% (n = 7) failed the otoscopic examination because of impacted cerumen, 13% (n = 6) of participants failed pure tone audiometry (Pta) screening across two or more frequencies and 72% (n = 33) failed both Pta and Distortion Product OAEs screening. Sixty-five per cent of participants (n = 39) were referred for diagnostic audiometry. Fifteen per cent (n = 7) were referred to the general practitioner for cerumen management.A total of 60 participants underwent a hearing screening test. Seventy-nine per cent of the participants were female. The racial distribution of the sample size consisted of blacks and whites, with the latter group comprising the largest percentage 91% (n = 31) provided an affirmative response. Of the total sample, both those with and without hearing aids (n = 70), 74% (n = 36) reported that the hearing problem negatively affects their lives. Results revealed that 29% (n = 16) of the participants felt depressed, worried and anxious as a result of their hearing difficulties. This was followed by a total of 11% (n = 8) of the participants who reported feeling angry about their hearing difficulties. A total of 10% (n = 7) felt a sense of grief because of their loss of hearing. Twenty per cent of participants felt unaccepted by their significant others as a result of their hearing impairment.The 60 participants who underwent hearing screening were asked if they perceived themselves as having a hearing problem and of these 51% (n = 55) of participants stated yes to the question relating to social participation in that they continue to partake in social gatherings and meetings held at homes and religious gatherings. However, 29% of participants (n = 20) reported that their communication partners do get angry and frustrated with them as a result of the hearing problem. In terms of localisation, 66% (n = 46) reported that they were able to identify where sounds originated from in the environment, and 33% (n = 36) reported challenges with speech discrimination over the phone. A Chi Square test was conducted to determine the relationship between the screening result (n = 60) and QoL responses. Hearing difficulties were significantly associated with a reduced QoL . Of the 60 participants who were screened, 63% (n = 38) stated that they had not heard of an audiologist before.Regarding social interaction, a total of 78% (n = 10) cited challenges with dexterity issues, acoustic feedback and discomfort as reasons for disuse of the hearing aid. Ninety per cent (n = 9) of the participants said that since using their hearing aids, their communication abilities improved in terms of sound localisation and listening abilities in the presence of background noise. Six (60%) of the participants mentioned an improvement in localisation to sound since receiving their hearing aids. Eight of the 10 participants further reported an overall improvement in QoL since receiving and utilising their hearing aids, and two of the 10 participants reported challenges with maintaining their hearing aids in terms of changing the batteries and with cleaning their device.All 10 participants who wore hearing aids were fitted with digital hearing aids. Eight of the 10 (80%) participants reported that they used their hearing aids daily with two out of the 10 (20%) saying that they use them infrequently. All participants  and self-reported reduction in QoL. Joore and colleagues  demonstrCiorba and colleagues  as well Overall, the results of the present study corroborate with those of Salonen and colleagues , where tA high prevalence of undiagnosed and poorly managed hearing impairment in the elderly residing in retirement homes is a significant problem. Hearing impairment has an impact on the social, psychological and communication aspects thereby reducing QoL. Audiologists need to solidify their roles and responsibilities for the management of ARHL and ensure that the vulnerable ageing population is adequately provided with the knowledge, resources and services to effectively manage their hearing disorders to reduce the negative impact that ARHL can have on QoL.Future research is required on the development and feasibility of geriatric hearing screening programmes, particularly for use within retirement home facilities. These programmes should ideally be multidisciplinary, offering evaluation and monitoring of QoL, practical coping mechanisms and psychosocial support, alongside audiological management in order to remediate the progression of the disorder and subsequently impact on the QoL of the elderly in these facilities. Further research into the outcomes of a collaborative approach of different professionals in the management of hearing loss in retirement homes would be warranted. This is important as the progression of presbycusis cannot be prevented, therefore, early identification and subsequent management of the hearing impairment is essential . Limitations of the study included the small sample size that hindered the generalisation of findings. Furthermore, a comparison of services and QoL outcomes within the private and state homes could not be conducted for this study because of the uneven distribution between both contexts. In addition, more qualitative studies looking into experiences of the current population involving hearing and their QoL as well as interviewing professionals to also assess reasons behind poor or neglectful care, including lack of follow-up, is required.


Sensorineural hearing loss is a common sensory impairment in humans caused by abnormalities in the inner ear. The stria vascularis is regarded as a major cochlear structure that can independently degenerate and influence the degree of hearing loss. This review summarizes the current literature on the role of the stria vascularis in the pathogenesis of sensorineural hearing loss resulting from different etiologies, focusing on both molecular events and signaling pathways, and further attempts to explore the underlying mechanisms at the cellular and molecular biological levels. In addition, the deficiencies and limitations of this field are discussed. With the rapid progress in scientific technology, new opportunities are arising to fully understand the role of the stria vascularis in the pathogenesis of sensorineural hearing loss, which, in the future, will hopefully lead to the prevention, early diagnosis, and improved treatment of sensorineural hearing loss. Hearing loss is the most common sensory deficit in humans and has a negative influence on 430 million people worldwide, including 34 million children . Most caThe SV is located in the lateral wall of the cochlea, connected externally with the spiral ligament, and internally with the endolymph. The SV is mainly composed of marginal, intermediate, and basal cells . The strOne of the significant functions of the SV is to generate the endocochlear potential (EP), which is essential for audition. It is believed that EP is generated by the transport of potassium from SV into the endolymph  in a proAnother important function of the SV is to regulate the secretion of the endolymph and maintain cochlear homeostasis . Among tA preliminary literature search up to April 2021 was performed using PubMed, using the retrieval formula “(sensorineur*[Title/Abstract]) AND (hearing[Title/Abstract]) AND (stria vascularis[Title/Abstract])”. The obtained papers were classified by etiology according to the title and abstract. Next, the term “stria vascularis” was combined with the following key-words for further search: hereditary hearing loss, drug-induced hearing loss, age-related hearing loss, noise-induced hearing loss, autoimmune inner ear disease, and systemic disease. Subsequently, irrelevant articles were eliminated and the remaining articles were examined and elaborated on. In addition, the reference lists of the included articles were manually searched for further applicable sources.The SV plays an important role in HHL pathogenesis. Several researchers have previously summarized the histopathologic findings associated with these genetic mutations, and atrophy or fibrosis of the SV has been observed in many cases, often caused by mutations in GJB2, COCH, and MYH9, as well as by Usher syndrome, and Alport syndrome . SyndromMutations in the potassium channel subunit KCNQ1 cause Jervell and Lange-Nielsen syndrome, while potassium channels in the SV play an important role in maintaining EP . ResearcMost cases of congenital SNHL are non-syndromic. The a4 subunit is a component of the multi-subunit proton pump (H + -ATPase), and mutations in the ATP6V0A4 gene lead to autosomal recessive distal renal tubular acidosis in patients who often show sensorineural hearing impairment. Lorente de Nó et al. studied the inner ear phenotype of Atp6v0a4 knockout mice and observed severe expansion of the scala media, a flattened and thinner SV, and a lack of endocochlear potential, suggestive of defects in SV function. Atp6v0a4−/− mice showed elevated thresholds in auditory brainstem responses. These findings help to understand the role of Atp6v0a4 expression in the ear and may contribute to the development of effective treatments for distal renal tubular acidosis (dRTA)-associated deafness .BDP1 is a member of the TFIIIB complex, which plays a key role in transcription by RNA polymerase III . This miCurrently, more than 150 drugs are known to be ototoxic and can cause functional impairment and/or cellular degeneration of tissues of the inner ear, leading to SNHL . The traSome studies only observed structural abnormalities of SV after treatment with ototoxic drugs, and speculated that the SV was the site of injury to ototoxic drugs. For example, researchers applied drugs such as mitomycin C or taxol to animals, and found degenerative changes in the cochlea, including vacuolization in the SV and a decrease in the number of fibroblasts. Therefore, researchers speculated that subsequent hearing loss in animals is associated with SV .The pathophysiological mechanisms of drug-induced SV dysfunction are poorly understood, although several studies offer some insights. A significant decline in EP is often observed in patients with drug-induced hearing loss. Recently, damage of the Na, K-ATPase, Na-K-2Cl-Cotransporter-1 (NKCC1), and potassium channel KCNQ1, which are related to EP generation, have received attention . In a moAt present, the cellular and molecular mechanisms underlying SV injury caused by ototoxic drugs are still unknown, and the pathogenesis of different drugs is not identical. Ion channels in SV are still considered a crucial target for future investigations; inflammation may also be a promising target to prevent and treat drug ototoxicity. However, the detailed mechanisms remain to be investigated.Historical studies have suggested that age-related hearing loss (ARHL) involves a number of auditory structures and mechanisms , includiOne study investigated the morphological changes in the SV of aged mice using TEM, which revealed that the SV in the aged cochlea was degenerated, with a large number of vacuoles and enlarged intercellular spaces . HoweverSeveral mechanisms underlying SV dysfunction in ARHL have been described, including mitochondrial dysfunction, ion transport channel damage, oxidative stress, and inflammation. Lyu et al. observed damaged mitochondria with disorganized dysmorphic cristae and decreased cytochrome C oxidase I (COX1) levels in aged SV, indicating mitochondrial morphological damage and dysfunction . Spicer Because of their important role in generating and maintaining cochlear potential, K+ channels have been repeatedly studied . HoweverLuz and Jiang conducted experiments in SV-k1 cell lines (from SV) and primary marginal cells of the SV, respectively , to explIn the current research, TEM and partial corrosion casting provide a more intuitive understanding of the morphological changes of SV, including some details of vessels in the cochlea. Although there is abundant research on the mechanism of SV dysfunction in ARHL, the exact biological mechanism remains unknown, and thus requires further exploration.Noise-induced hearing loss (NIHL) is one of the most common types of SNHL, affecting more than 600 million people worldwide . A previAbnormal cochlear microcirculation has long been considered a crucial cause of noise-induced hearing loss . NormallIt has previously been shown that NO-derived free radicals in the SV participate in the pathophysiology of NIHL . Shi et The role of inflammation in NIHL has also been investigated. Adhesion molecules mediate the adhesion and transmigration of leukocytes, and researchers have found that noise activates the expression of adhesion molecules in the SV to induce hearing loss, leading to speculation that inflammation might be one of the mechanisms by which noise impairs SV function. In addition, In addition, there are some other possible mechanisms that could benefit our understanding of the pathology of SV after acoustic trauma, such as abnormal pericytes of SV  and reguAutoimmune inner ear disease is a rare cause of SNHL , and itsDegeneration of SV has been observed in different autoimmune mouse models. Previous studies have reported the destruction of the cochlear BLB and immunoglobulin deposition in SV in C3H/lpr autoimmune mice, resulting in shifts in the ABR threshold . SimilarRuckenstein et al. conducted a series of studies on MRL-Fas(lpr) mice, which was proposed as a model of autoimmune inner ear disease. They further observed pathological changes in mouse SV, including hydropic degeneration of the SV, antibody deposition in the SV, and reduction in EP, but no reduction in the in Na, K-ATPase levels. Therefore, they inferred that the reduction of EP may occur as a result of cellular degeneration within the SV ,b, c. FuMost previous studies observed typical pathological changes in SV, such as edema degeneration and immunoglobulin deposition; however, investigation of the mechanism is lacking and further exploration will be needed in the future.The association between type 2 diabetes mellitus and hearing loss remains controversial . SNHL ofCongenital and acquired hypothyroidism can result in hearing loss , while iSeveral researchers have observed the cochlear structures in mice with hyperlipidemia and found profound edema in SV . When viSystemic diseases such as diabetes, hypertension, and hyperlipidemia can all cause hearing loss. However, current studies have only proven that the SV is the damaged site of the cochlea, while the underlying pathogenesis is still unknown.Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children  and its Temporary or permanent SNHL is a sequela of pneumococcal otitis media. Streptococcus pneumoniae meningitis, In Mongolian gerbils with Streptococcus pneumoniae may lead to SNHL. At present, it could be inferred that SV damage is related to hearing loss. However, the exact mechanism remains to be elucidated.Infection with CMV or The morphological changes and functional impairment of the SV are observed in the pathogenesis of SNHL. Some types of hearing loss share commonalities in their pathogenesis. For example, all ototoxic drugs must cross the BLB to enter the inner ear tissues to exert their cytotoxic effects and induce hearing loss; therefore, extensive vacuolization in the SV has always been observed in related investigations. Moreover, the inner ear has been considered an immune-privileged site because of the presence of BLB . AutoimmThe cochlea’s small size, fragility, and encasement in the densest bone in the body located deep within the skull make it difficult to dissect and explore ; thus, iAlthough the current research on the SV in SNHL is still fragmented and unsystematic, we believe that the SV plays an important role in SNHL and look forward to further investigations on the mechanisms underlying of SNHL, which should identify new targets for the prevention and treatment of SNHL.WY and SZ wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Arabidopsis thaliana; and the developmental and environmental regulation of anthocyanin accumulation. This review reveals the molecular mechanisms underlying anthocyanin biosynthesis in different plant species and provides valuable information for the development of anthocyanin-rich red-skinned and red-fleshed apple and pear varieties.Anthocyanins contribute to the quality and flavour of fruits. They are produced through the phenylpropanoid pathway, which is regulated by specific key genes that have been identified in many species. The dominant anthocyanin forms are reversibly transformed at different pH states, thus forming different colours in aqueous solutions. In plants, anthocyanins are controlled by specific factors of the biosynthetic pathway: light, temperature, phytohormones and transcription factors. Although great progress in research on anthocyanin structures and the regulation of anthocyanin biosynthesis has been made, the molecular regulatory mechanisms of anthocyanin biosynthesis in different plants remain less clear. In addition, the co-regulation of anthocyanin biosynthesis is poorly understood. In this review, we summarise previous findings on anthocyanin biosynthesis, including the biochemical and biological features of anthocyanins; differences in anthocyanin biosynthesis among fruit species, i.e., apple, red pear, and the model plant  The accumulation of different pigmentations affects the growth, development and reproduction of plants under various conditions, which, similar to the diversification of coat hair colour in mammals, is appropriate for different environments . AnthocyIn the past few decades, great progress in the understanding of anthocyanin metabolism in model plant species has been made, especially with respect to the biosynthetic pathways of these compounds. In plants, anthocyanin biosynthesis is affected by various biotic and abiotic stresses, including UV irradiation, insect attack, drought, and low temperature ,10,11. AAnthocyanins participate in the formation of fruit quality, affecting taste, colour and lustre, whilst even affecting human health. The biosynthesis of anthocyanins in fruit crops has attracted large amounts of attention from academics. With the development of molecular biology and bioinformatics, an increasing number of studies have revealed that there are obvious differences in the regulatory mechanisms of anthocyanin biosynthesis between different plant species. Many key players in the complex regulatory network remain to be identified. Therefore, this article aims to provide a detailed overview of the known regulatory mechanisms of anthocyanin biosynthesis in apples and pears and provide a theoretical foundation for the genetic improvement and breeding of crops, fruits and ornamental plant species .Anthocyanins are important secondary metabolites belonging to the flavonoids (polyphenols). At present, more than twenty kinds of anthocyanins have been identified in nature, and approximately 90% of more than 550 kinds of anthocyanins found in nature are derived from the six most common anthocyanins: cyanidin (Cy), peonidin (Pn), pelargonidin (Pg), malvidin (Mv), delphinidin (Dp) and petunidin (Pt). Anthocyanins exist alongside a variety of monosaccharides, including glucose, rhamnose, galactose and xylose, and disaccharides consisting of rhamnose, gentian disaccharide and sophora disaccharide to form glycosides. Additionally, anthocyanins consist of α-phenylbenzopyran cations and are mainly composed of C6(A)-C3(C)-C6(B) carbon skeleton structures . At the The corresponding four dominant anthocyanin forms, flavylium cations, carbinol pseudobases, neutral quinonoidal bases and chalcone, are reversibly transformed at different pH states , and so PAL) and 4-coumarate–CoA ligase (4CL); early biosynthetic genes (EBGs), such as chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), flavonoid 3′-hydroxylase (F3′H), and flavonoid 3′5′-hydroxylase (F3′5′H); late biosynthetic genes (LBGs), such as dihydroflavonol 4-reductase (DFR), anthocyanidin synthase/leucoanthocyanidin dioxygenase (ANS/LDOX), and UDP-glucose flavonoid glucosyl transferase (UFGT); and modifying genes, such methyltransferase (MT), O-methyltransferase (OMT) and anthocyanin transferase (AT). In addition, four structural genes, transparent taste 10 (tt10), transparent taste 12 (tt12), transparent taste 13 (tt13) and transparent taste 19 (tt19), encode polyphenol oxidase (PPO), a secondary transport factor of the MATE (multidrug and toxic compound extrusion) family, H (+)-ATPase and glutathione S-transferase (GST), respectively. These proteins play significant roles in the modification, transport and oxidation of anthocyanidins [Anthocyanins are synthesised from a common phenolic precursor through the phenylpropanoid pathway on the cytoplasmic face of the endoplasmic reticulum in plants. Stable anthocyanins formed by different modifications, such as glycosylation, methylation and acylation, are transported into the vacuole, where they accumulate. As one of the end-products of the flavonoid biosynthetic pathway, proanthocyanidins are synthesised from epicatechin, which is catalysed by anthocyanidin reductase (ANR) and subsequently transported and polymerised . The coryanidins ,23,24.The synthesis of anthocyanins in plants is controlled by regulatory genes. At present, the identified genes involved in the regulation of the anthocyanin biosynthetic pathway consist of the myeloblastosis family (MYB) TFs, the basic helix-loop-helix (bHLH) TFs and the tryptophan-aspartic acid repeat (WDR) TFs ,26. GeneThe biosynthesis of anthocyanins is affected by many factors, and therefore the regulatory mechanism is complicated in plants. To date, the main factors include environmental factors, phytohormones, transcription factors and epigenetic modification. A schematic of the regulatory mechanism of the activation of anthocyanin biosynthesis is summarised briefly . In planLight is essential for plant growth and development, and especially affects anthocyanin biosynthesis. After photostimulation, the photoreceptors activate a range of signal transduction pathways involving photoreactions and corresponding gene expression . In thisMdBBX37. MdBBX37 belongs to the zinc finger transcription factor family, whose members contain at least one conserved B-box motif in the N-terminal region [MdHY5 by directly targeting the promoter of MdHY5. Conversely, MdWRKY72 and MdWRKY11 transcription factors bind to the W-box cis-element of MdHY5 to activate its regulation of anthocyanin biosynthesis [MdMYB1/10 [In apples A, light l region ,39. MdBBynthesis ,40. Thusynthesis ,37. MoredMYB1/10 . HoweverdMYB1/10 ,42,43.PpMYB10 promoter, but whether PpHY5 can activate gene expression has not been proven [PpMYB10 and subsequently strongly enhances light-induced anthocyanin accumulation, and the overexpression of PpBBX16 also promotes anthocyanin accumulation in the peel of pear fruits [PpMYB10 transcription [MYBD promoter directly in A. thaliana, which positively accelerates the expression of downstream genes in light- or cytokinin-stimulated signalling pathways [In red pears, PpBBX16, a positive regulator of light-induced anthocyanin accumulation, cannot combine directly with the promoter of either PpMYB10 or PpCHS, but can interact with PpHY5 physically to form the PpBBX16-PpHY5 complex B. PpHY5 n proven . The PpBr fruits . As a pocription ; converscription ,47. In apathways ,48,49.A large number of studies have also revealed that ambient temperature is a key factor regulating the accumulation of anthocyanins. In general, high temperature represses while low temperature promotes the biosynthesis of anthocyanin ,51,52. IA. thaliana, JAZ (jasmonate ZIM-domain) proteins are substrates of the SCFCOI1 complex, which interferes with the transcriptional levels of WD/bHLH/MYB complexes by interacting directly with the C-terminus of both bHLH and MYB members, in turn repressing anthocyanin biosynthesis [MdMYB9 promoter, which represses the transcription of the MBW complexes and further decreases anthocyanin biosynthesis [PpMYB10 and PpMYB114) and LBGs (late biosynthetic genes) in red pears, and ethylene signal transduction occurs via ethylene response factors (ERFs) and EIN3/EILs  [Arabidopsis thaliana, while GA signalling curbs anthocyanin biosynthesis via DELLA proteins [Phytohormones are indispensable for the processes of plant growth and development, and known plant hormones, such as JA (jasmonate), ABA (abscisic acid), ethylene and auxin, could stimulate the ethylene response factor family (ERF) and be involved in the regulation of anthocyanin biosynthesis ,56,57. Iynthesis . Moreoveynthesis . The dirynthesis . In addiynthesis . Ethylenke, EIL) ,61. Cytoproteins ,63. DELLproteins .MdMYB1 is positively correlated with the accumulation of anthocyanin and the expression of structural genes because the MdDFR and MdUFGT promoters include light-response elements, such as ACGTs and MRE or MRE-like sequences [MYBL2 is reduced, the expression of early biosynthetic genes and the accumulation of anthocyanin increase  in poplar and Arabidopsis [Demethylation and methylation of DNA also have important roles in regulating anthocyanin accumulation, and studies have shown that the DNA methylation inhibitor 5-azacytidine can induce red pigmentation in apple and peach fruits ,75. Coinbidopsis ,79,80. Mbidopsis .A. thaliana, there are still obvious differences in the regulatory mechanism of anthocyanin biosynthesis between different plants. For example, BBX proteins are a link between light signals and HY5 in apples and pears, but PHYTOCHROMES B (PHYB) functions as a “bridge” connecting light stimulus and HY5 in A. thaliana. Therefore, it is necessary to elucidate the regulatory mechanisms of anthocyanin biosynthesis in different plant species.Anthocyanins protect against abiotic and biotic stresses in plants, and optimising anthocyanin content is regarded as the goal of breeding programmes in apples and pears. Many factors, such as light, transcription factors, phytohormones, affect the anthocyanin accumulation in plant tissues. Although HY5 and the MBW complex play core roles in anthocyanin biosynthesis in apples, pears and In addition, as follows, there are other problems that also remain to be studied: (1) although the biosynthesis and accumulation of anthocyanins are reportedly regulated by environmental factors, plant hormones, structural genes and regulatory genes, their interrelationships in this pathway need to be further explored. (2) What kind of transcription factor modifications exist in the dynamic balance of anthocyanin synthesis and degradation? Four dominant anthocyanin forms are reversibly transformed at different pH states and affect the colour of aqueous solution. However, what is the mechanism by which pH affects anthocyanin transformation? (3) Current research is limited to the molecular level, but as science and technology progresses, we can strengthen integrated genomic, phenotypic genomics, proteomic, and metabolomic research and use a variety of means to explore unknown parts of anthocyanin regulatory mechanisms and metabolic pathways in apple and pear, and then reveal relationships among anthocyanin and colour, sugar content, and other flavour attributes. In addition, to put this information in perspective, the mechanisms involved in the function of the MBW complex are highly conserved during the regulation of anthocyanin biosynthesis in higher plants, but mechanisms related to environmental and developmental factors affecting anthocyanin biosynthesis are complicated, even the information based on these mechanisms from different species is very fragmented. Thus, additional regulatory pathways and key genes and proteins during the process of anthocyanin biosynthesis in crop, ornamental and other fruit species would also be worthwhile for further investigation.Overall, with the deepening of research, we will have a clearer understanding of the mechanism of anthocyanin synthesis and accumulation, therefore establishing a stable genetic transformation system using gene engineering technology to improve plant colour, which will provide a solid technology and information basis for crop breeding and mechanised intensive planting in the future.


The Biological Market Theory (BMT) posits that cooperation between non-human animals can be seen as a mutually beneficial exchange of commodities similarly to what observed in human economic markets. Positive social interactions are commodities in non-human animals, and mutual exchanges fulfilling the criteria of the BMT have been shown in several species. However, the study of biological markets suffers from methodological limitations that are mainly linked to the difficulty of clearly identifying the currencies and their exchanges in the short-term. Here, we test whether bonobo females are more attractive during their maximum swelling phase, whether they exchange grooming and Genito-Genital Rubbing (GGR) on a daily level of analysis, and whether these daily exchanges fulfil the BMT criteria. Females engaged more in GGR when their sexual swelling was in the maximum phase. Moreover, they exchanged grooming and sex according to the daily “market fluctuations” associated with swelling status. Females in the minimum phase  increased their probability to engage in GGR with females in the maximum phase  by grooming them preferentially. In line with the supply/demand law, the female grooming strategy varied depending on the daily number of swollen females present: the higher the number of swollen females, the lower the individual grooming preference. As a whole, our study confirms BMT as a valid model to explain daily commodity exchanges as a function of the temporary value of traders, and underlines the importance of a day-by-day approach to unveil the presence of a biological market when the value of traders frequently changes. Within this context, a commodity must be monopolizable and cannot be obtained by force, so that individuals should develop an alternative strategy to conflict to get the commodity2. Within the same class of traders, individuals are chosen as partners depending on the commodities available on the market, therefore the best strategy is either to increase the value of the commodity offered, or to demand less in return in order to outcompete the other traders3. As it occurs in human markets4, the exchange rate of commodities in a Biological Market depends on the law of supply and demand: when a certain commodity is rare, competition over it is high, as its value is perceived as being high as well. Under these circumstances, the other individuals are inclined to “pay more” to get the rare high-value commodity3.The Biological Market Theory (BMT) posits that cooperation between non-human animals can be seen as a mutually beneficial exchange of commodities (i.e. goods or services) similarly to what is observed in human economic markets5; red bishops, Euplectes orix6; wood mice, Apodemus sylvaticus7; meerkats, Suricata suricatta8).Social interactions are a valuable commodity in non-human animals, and mutual exchanges fulfilling the criteria of the BMT have been shown in several species . Allo-grooming is a frequent and valuable behaviour among primates where it can serve the functions of reinforcing social bonds14, fostering coalitions15, and reducing tension16. As highlighted by Sánchez-Amaro and Amici17, the study of biological markets in primates suffers from theoretical and methodological limitations that are mainly linked to the difficulty of identifying clear exchanges in cognitively and socially complex species. Indeed, primates are capable of keeping track of both short- and long-time exchanges18 and live in markets where social commodities are not only highly variable but also strongly interconnected19. Concerning the temporal scale, there is a total lack of studies focussing on the exchanges on a daily level of analysis.The BMT has also been used to explain several types of short- and long-term exchanges in non-human primates (hereafter primates), with most studies focusing on allo-grooming as a commodity to exchange  to fill this gap by exploring the possible existence of a biological market regulating the exchanges of social interactions in females living in two stable social groups. To reach this goal, we focussed our analyses on the daily fluctuation of grooming and socio-sexual interactions as a function of the swelling status of actor and receiver. As far as we know, it has never been demonstrated that the Biological Market Theory explains the exchange of commodities in bonobos, although it has been hypothesized20.Here, we focus on the bonobo (Pan troglodytes), bonobos are human closest living relatives. The two Pan species live in multi-male/multi-female social groups characterized by fission–fusion dynamics and show male philopatry and female dispersal21. This dispersion pattern causes a higher level of relatedness among males than among females, nevertheless bonobo females are highly cohesive and share strong affiliative bonds24. Female cohesiveness and affiliation allow bonobo females to be dominant over males—or co-dominant according to some authors25—which is a notable exception in a male-philopatric species26. Female bonds are established and maintained through a wide array of affiliative behaviour such as play27, consolation28, agonistic support23, allo-grooming26, face engagement29, and socio-sexuality30. Bonobos are well known for making use of sexual behaviour for social purposes and, particularly, to decrease social tension during competitive contexts, such as food distribution or aggressive interactions31. Bonobo females frequently engage in Genito-Genital Rubbing (GGR), a socio-sexual behaviour during which females embrace each-other, frequently face to face, and rub their genitals by moving their hips side to side32. Recently, Moscovice et al.30 showed that GGR plays an essential role in enhancing female cooperation as this behaviour stimulates the release of oxytocin. Moreover, this face-to-face interaction favours the perception and replication of facial expressions through the phenomenon of Rapid Facial Mimicry (RFM33). RFM is an unconscious phenomenon that represents a basic layer of empathy34 and is a powerful mechanism that helps establishing an emotional bridge between two subjects.Together with chimpanzees .36, we predict GGR rates to be higher when at least one of the females in the dyad is in the maximum swelling phase.For a biological market to be established, it is necessary to first demonstrate that a desirable resource is present. If the maximum swelling phase increases the attractiveness of females and the motivation to engage in GGRPrediction 2a). Moreover, we expect dyadic grooming preference to vary on a daily basis as a function of actor’ and receiver’s swelling state (Prediction 2b).If grooming is a commodity that is exchanged on a daily basis, we predict that grooming rates show daily fluctuations following the supply/demand law. Specifically, we expect female grooming rates to decrease as the number of available females in maximum swelling phase increases (Prediction 3a). Moreover, we expect GGR to be influenced by both the daily grooming rate (commodity) and the swelling phase . Specifically, we predict the positive effect of grooming on the frequency of GGR to be maximum when the actor is in the minimum and the receiver is in the maximum swelling phase (Prediction 3b).If grooming and GGR are commodities that are exchanged according to the BMT, we expect the daily frequency of GGR to fluctuate as a function of the number of females showing maximum swelling (supply/demand law) . Since the study was purely observational with no human-animal interaction and/or manipulation whatsoever, the committee waived the need for an ethical permit.The study was part of a long-term research project on bonobo social behavior. Data were collected at the Apenheul Primate Park  and at La Vallée des Singes  where bonobos lived in inter-connected indoor enclosures with free access to an outdoor naturalistic forested island , 6 days a week from 9:00 to 18:00. The group was composed by 5 adult females, 4 adult male, and 1 immature subject (see Supplementary Information).39.In Apenheul, behavioural data were collected by using a voice-recorder and were then transcribed on database sheets. The techniques used were Focal Animal Sampling  and All Occurrences Sampling 39 for a total of 166 h of videos. The Focal Group Sampling method consists in randomly selecting a sub-group of subjects and recording their behaviours. In our case, we applied this methodology to collect the videos. Videos were then analysed and transcribed on database sheets. The techniques used to analyse the videos were: Focal Animal Sampling  and All Occurrences Sampling (200 h)39.In La Vallée des Singes, behavioural data were collected by using camcoders and by applying the Focal Group Sampling methodFor both groups, allo-grooming sessions were collected through the Focal Animal Sampling method and were used to establish grooming preference. Sexual and agonistic interactions were collected through the All-Occurrences Sampling method and the latter were used to determine group hierarchy (see below for hierarchy estimation). Kinship through the maternal line was known.40.Data were collected and analysed according to a blind coding protocol in which the observers were not aware of the hypotheses and predictions that would have been tested. Before systematic data collection and video analyses, the observers and coders underwent a training phase during which they followed the same focal animal simultaneously and then compared data. The training phase lasted until the Cohen’s Kappa values measured for all the behaviours defined in Supplementary Table Daily observations of perineal swelling and menstruation were carried out by the bonobo keepers. Keepers from Apenheul Primate Park recorded daily appearance of sexual swelling stage, according to the following rating system: 1 ; 2 ; 3 and 4 ; and 5 . Using the same parameters, keepers from La Vallée des Singes recorded daily appearance of sexual swellings stage according to the following rating system: 1 ; 2 ; 3 ; and 4 . For data unification, we standardized sexual swelling phases in two categories: minimum (phase 1 + 2) and maximum swelling phase . For each adult female showing monthly variations in the swelling cycle  divided by the sum of the daily directional grooming duration performed by the same individual towards all other subjects including B [A grooms (B + C + D)]. The daily grooming preference therefore expresses the proportion of time that one individual spends grooming another one, weighted on the total amount of grooming provided by the same subject on a daily basis. Our study focused on individuals offering grooming, so polyadic grooming sessions were split into dyadic grooming sessions when the focal individual was receiving grooming from multiple partners. It is nevertheless worth noting that polyadic grooming sessions are relatively infrequent in bonobos and very rare among bonobo females42). NDS were calculated on the basis of a dyadic dominance index (Dij) in which the observed proportion of wins (Pij) is corrected for the chance occurrence of the observed outcome. The chance occurrence of the observed outcome was calculated on the basis of a binomial distribution with each animal having an equal chance of winning or losing in every agonistic encounter42. The correction is necessary when the interaction numbers greatly differed across dyads.We evaluated hierarchical relationships on the basis of dyadic and decided conflicts that occurred over the whole period of observation by using a winner/loser matrix to assess the rank according to the Normalized David’s Scores . We estimated the individual frequency of GGR per day for each swelling phase . We used the software Resampling Procedures 1.3 by David C. Howell (freeware), that provides a t-value  when comparing two dependent groups, with the probability to obtain such values under the null hypothesis.To compare GGR frequencies of dyads involving females in the minimum swelling phase to dyads involving at least one female in the maximum swelling phase, we ran a paired randomization test at the dyadic level with a number of 10,000 shuffles  to avoid errors due to non-independence of the data44) using the RStudio interface (version 1.3.95945). Prior to fitting the model, all the covariates were z-transformed to a mean of 0 and a standard deviation of 1 to achieve more easily interpretable estimates and facilitate model convergence46. To rule out collinearity we determined Variance Inflation Factors (VIFs) using the function vif of the R package car (version 3.0-347) applied to a standard linear model excluding the random effects and the interactions. Both Model 1 and Model 2 presented below have been tested with the inclusion of female parity as factor shaping grooming preference and GGR. However, due to very high collinearity with actor and receiver’s age  we excluded them from all the analyses. After removal of parity, all the VIF values were considered acceptable (maximum VIFs across models = 3.31). Model stability was assessed using a function that excluded the levels of the random effects one at a time48. For all models, we performed a full vs control model comparison, with the control model containing only random effects, random slopes and control predictors to test whether the inclusion of explanatory predictors improved model fit. Tests of the individual predictors were derived using likelihood ratio tests49 (R function drop1 with argument ‘test’ set to “Chisq”). We conducted post-hoc comparisons using Tukey tests, and report only significant tests.We ran all Generalized Linear Mixed Models (GLMM) models in R  and Prediction 2b (effect of actor’ and receiver’s swelling state on daily dyadic grooming preference). Model 1 investigated whether daily grooming preferences (as dependent variable) varied depending on the following predictors: the daily number of females in the maximum swelling condition, the sexual swelling condition  of actor and receiver as well as their two-way interaction, and the group . Parity was not included due to high collinearity with age (see above). Considering the response range 0–1, we modelled it with a Beta error distribution and logit link function after data transformation which excluded exact values of 0 and 150. The number of females with the maximum sexual swelling included all the studied females that a given actor could access a given day. We included as control predictors the two-way interaction of actor and receiver’s age (numeric) and the two-way interaction of actor and receiver’s rank (continuous variable). We included the two-way interaction of actor and receiver’s rank to control for a possible influence of rank similarity/dissimilarity on the daily grooming preference. We included the two-way interaction of actor and receiver’s age to control for a possible influence of age similarity/dissimilarity. We removed non-significant two-way interactions and tested their main predictors. Identity of actor, receiver and dyad were included as random effects. We excluded random slopes due to convergence issues. Model 1 included 94 cases of daily grooming preferences involving 16 different dyads. In a given dyad AB, the grooming preference of subject A towards B is not equal to the preference of B towards A, allowing our model to estimate the effect of AB controlling for BA, and vice versa.We ran Model 1 to test Prediction 3a  and Prediction 3b (effect of daily grooming preference on the daily frequency of GGR depending on actor’ and receiver’s swelling phase). Model 2 investigated the effect of the number of swollen females, daily grooming preference (continuous variable) and sexual swelling  on the daily occurrence of GGR (numeric), by considering the directionality of the interaction. We modelled the response with a Gamma error distribution and log link function. To calculate the occurrence of GGR, we analyzed the successful sexual invitations  performed by the actor towards the receiver. Gestures, body postures and facial expressions used as sexual invitations are listed and described in Supplementary Table Parity was not included due to high collinearity with age (see above). We included as control predictors the two-way interaction of actor and receiver’s age and the two-way interaction of actor and receiver’s rank. We removed the not significant two-way interaction ageact*agerec and repeated the model to assess the effect of main age predictors. Identity of actor, receiver and dyad were included as random effects and the number of swollen females and grooming preference as random slopes. Because Model 2 did not converge, we excluded from the random slopes grooming preference and re-ran Model 2 successfully. Model 2 included 74 cases involving 13 dyads.We ran Model 2 to test 9 = − 2.275, P = 0.027) (Prediction 1 supported).Females engaged significantly less in GGR when they were both in the minimum swelling phase (mean ± SD: 0.32 ± 0.60), compared to when at least one female of the dyad was in the maximum swelling phase (mean ± SD: 0.61 ± 0.69) . The model did not include the non-significant interactions of ageact*agerec (p = 0.746) and rankact *rankrec (p = 0.726) and assesses the effect of age and rank as main control predictors. The daily grooming preference was significantly affected by the number of swollen females available the same day: the higher the number of swollen females, the lower the daily grooming preference (Prediction 2a supported) .Overall, the predictors Grooming*Swellingact*Swellingrec had an effect on daily GGR distribution after controlling for rank and age . The model did not include the non-significant interaction of ageact *agerec (p = 0.707) and assesses the effect of age as main predictors. The daily GGR occurrence was significantly affected by the number of females in the maximum swelling phase: the higher the number of swollen females, the lower the GGR occurrence . Moreover, the daily GGR occurrence was significantly affected by the three-way interaction of daily grooming preference and sexual swelling phase of both the actor and the receiver  when at least one female of the dyad was in the maximum swelling phase, compared to when both of them were in the minimum swelling phase (Prediction 1). When in the maximum swelling phase, females are more attractive for both males and females and tend to be invited more frequently to engage in sexual interactions than females in the minimum swelling phase26. This is in line with the hypothesis proposing that the peculiar features of bonobo females’ sexual swelling, and in particular its extremely long duration and presence during anovulatory periods, might have been selected to increase female-female sexual interactions35. Socio-sexuality in bonobo females help establishing and maintaining strong social bonds which, in turn, allow them to form coalitions that increase their social status and centrality30.Taken together, our results confirm the key role of sexual swelling in bonobos and provide new insights on the exchange of grooming with sex on a daily basis. More particularly, our study shows that grooming and sex represent valuable exchange commodities for bonobo females and that their exchange fluctuates depending on females’ sexual swelling status. These daily fluctuations can be explained by the supply/demand lawPrediction 2a, Fig. swellingact*swellingrec showed higher grooming preference when both the actor and the receiver were in the maximum swelling phase, compared to when the actor was in the minimum and the receiver was in the maximum swelling phase. These results confirm the higher attractiveness of females showing the maximum swelling phase , suggest that females tend to exchange grooming for grooming when their value is “low” (MIN) and that high-value females (MAX) prefer “high-value” grooming partners as well.According to the Biological Market Theory derived from the Market Theory applied in economics, the exchange rate of commodities depends on the supply/demand law, and when a certain commodity becomes common, its perceived value decreases. Consistent with the supply/demand law, the daily grooming preference was significantly affected by the number of females showing the sexual swelling at the maximum phase during the same given day: the higher the number of swollen females, the lower the daily grooming preference  and there are some indications that high-ranking and older females are preferred grooming partners55. Subjects within the same group may therefore compete for grooming access to high-ranking groupmates, since those can be the best coalition partners54. Alternatively, a grooming distribution related to rank can be explained by females’ preference in grooming subjects of similar social class  as an adaptive strategy derived from greater compatibility between subjects56. These mechanisms are beyond the aim of our investigation but can still drive the variation of grooming preferences and mask the effect of the daily market. For this reason, we included in our models rank and age of both actor and receiver as control predictors. However, our results on the daily grooming preference showed no effect of actor and receiver’s rank and age, suggesting that the factors shaping grooming preference among bonobo females on a daily basis may not coincide with those affecting such preference on the long term. Moreover, it has been showed that the steepness of the hierarchy varies between different bonobo groups in captivity25. Particularly, these studies demonstrated that grooming was preferentially directed towards dominant individuals in those groups where the hierarchy was very steep, whereas grooming was more reciprocal in those groups showing a mild hierarchy. It is worth noting that the steepness of our study groups was extremely low .In many primate groups, higher-ranking subjects typically receive more grooming than lower-ranking onesPrediction 3a). Post-hoc analyses revealed no significant effect of grooming preference on the daily occurrence of GGR when the actor was in the maximum swelling condition and the receiver was in the maximum or minimum swelling condition  attractive, females in the minimum swelling phase must augment the commodity they provide to increase their possibility of engaging in sexual interactions with higher-value females. Furthermore, by strategically offering more grooming, lower-value females can even outcompete higher-value ones to gather “sexual favours” from the most attractive partners.In conclusion, our study confirms the BMT in explaining the daily exchange of commodities and its fluctuations as a function of the temporary value of traders, and underlines the importance of a day-by-day approach to unveil the presence of a biological market when the value of traders rapidly changes.Supplementary Information 1.Supplementary Information 2.


Leptodactylus fallax) is a critically endangered frog native to the Caribbean islands of Dominica and Montserrat. Over the past 25 years their populations have declined by over 85%, largely due to a chytridiomycosis outbreak that nearly wiped out the Montserratian population. Within the context of developing tools that can aid in the conservation of the mountain chicken frog, we assembled its complete mitochondrial genome, contributing the first complete mitogenome of the genus Leptodactylus (Genbank Accession number MW260634). The circular genome is 18,669 bp long and contains 37 genes. A phylogenetic analysis reveals that L. fallax forms a clade with Leptodactylus melanonotus, highlighting the close relationship of Leptodactylus spp. relative to other species from the superfamily Hyloidea included in the analysis.The mountain chicken frog ( Leptodactylus fallax Müller, 1926), endemic to the Lesser Antilles, is one of 83 species in the genus Leptodactylus (Frost 2021). As a giant frog with a large appetite, L. fallax plays an important ecological role as a native apex predator in its remaining home range on Montserrat and Dominica  in March 2009. The sample is stored in the archive of the Molecular Ecology Lab, Cardiff University School of Biosciences, under voucher ID L2175. DNA was extracted using a QIAGEN DNeasy Blood & Tissue Kit protocol for nucleated blood. Whole genome paired-end Illumina sequencing was performed by Novogene, Hong Kong. A subsample of the raw Illumina paired-end reads was produced using the Novoplasty filter_reads.py script with L. melanonotus were identical.The mitogenome consisted of 42.8% GC, with individual base percentages at: A − 29.7%, C − 28%, G − 14.7%, and T − 27.5%. Annotation was guided using MITOS web server , 8 members of the same superfamily Hyloidea, and one distantly related anuran species from the genus Odorrana (Leptodactylus fallax and L. melanonotus formed a clade with bootstrap support of 100. The nearest relation based on the alignment was the other member of the Leptodactylidae family, P. thaul, and a member of the Telmatobiidae family, T. chusmisensis, a Chilean endemic.A maximum likelihood phylogeny was constructed using the 13 concatenated protein coding genes of the mitogenome of Odorrana . Sequenc


We assessed the association of self‐reported hearing impairment and hearing aid use with cognitive decline and progression to mild cognitive impairment (MCI).We used a large referral‐based cohort of 4358 participants obtained from the National Alzheimer's Coordinating Center. The standard covariate‐adjusted Cox proportional hazards model, the marginal structural Cox model with inverse probability weighting, standardized Kaplan‐Meier curves, and linear mixed‐effects models were applied to test the hypotheses.P = .004) and an accelerated rate of cognitive decline (P < .001). Hearing aid users were less likely to develop MCI than hearing‐impaired individuals who did not use a hearing aid . No difference in risk of MCI was observed between individuals with normal hearing and hearing‐impaired adults using hearing aids .Hearing impairment was associated with increased risk of MCI (standardized hazard ratio [HR] 2.58, 95% confidence interval [CI: 1.73 to 3.84], Use of hearing aids may help mitigate cognitive decline associated with hearing loss. The growing evidence from observational studies shows that hearing aid use is associated with better cognition, slower cognitive decline,Hearing loss is associated with higher risk of mild cognitive impairment (MCI).Hearing loss is associated with accelerated cognitive decline.Hearing aid use is associated with lower risk of MCI and slower cognitive decline.People with normal hearing and hearing aid users have similar risk of MCI.Quality audiology screening might prove an effective dementia prevention strategy.Systematic Review: The authors reviewed the literature using PubMed. Although several studies evaluated the relationship between hearing impairment and cognitive decline, only two studies, with contradictory findings, have assessed the risk of developing mild cognitive impairment (MCI) in adults with and without hearing loss. The longitudinal studies investigating the association between hearing aid use and cognitive decline are scarce while no study has examined the role of hearing aids in healthy‐to‐MCI conversion.Interpretation: Our findings show that hearing loss increases the risk of incident MCI while hearing aid use robustly reduces progression to MCI. Our findings highlight the importance of taking a proactive approach toward addressing hearing decline over time.Future Directions: The article proposes a framework for the generation of new hypotheses. Examples include randomized clinical trials further exploring the relationship between auditory impairment and cognition and the hypothesized mechanisms that could account for this association.Although there have been many studies that included cognitively normal adults as part of the study sample, when investigating the association between hearing loss and cognitive decline or dementia as an outcome, few studies have examined the impact of hearing impairment and hearing aid use on incident MCI.The aim of the present study was 3‐fold: (1) to examine the impact of hearing impairment on cognitive function and progression to MCI in cognitively healthy individuals; (2) to investigate the relationship among the use of hearing aids, incident MCI, and cognitive decline; and (3) to compare time to incident MCI and rate of cognitive decline between individuals with normal hearing and hearing‐impaired participants that used hearing aids.22.1The cohort we studied were volunteers followed up approximately annually at National Institute on Aging‐funded Alzheimer's Disease Research Centers (ADRCs). The National Alzheimer's Coordinating Center (NACC) maintains a database of standardized clinical and neuropathological information collected from these ADRCs.2.2MCI incidence was determined based on the clinical diagnosis made by a single clinician or through a consensus process. Diagnoses of MCI were established using the modified Petersen criteria.Self‐reported hearing loss was evaluated through the response to the single question, “Without a hearing aid(s), is the subject's hearing functionally normal?” No information on the degree of hearing loss was provided in the NACC‐UDS. Although it was not reported to NACC whether participants with hearing impairment were wearing their hearing aids during cognitive testing, ADRCs were expected to use missing codes if it was indicated that hearing loss affected test performance. Records with missing codes were excluded from the analysis. Hearing aid use was also established based on self‐report. Hearing aid users were subsequently asked if the hearing aid provided them with “functionally normal hearing.” The positive response to this question implied that a participant did not demonstrate a reduced ability to carry out everyday activities, such as listening or talking, when wearing a hearing aid. All considered participants using hearing aids reported functionally normal hearing when wearing a device.2.3t‐test and Wilcoxon rank sum test to examine bivariate associations between predictor variables and outcomes for normally and non‐normally distributed continuous variables, respectively. The Shapiro‐Wilk test was used to determine whether the data significantly deviated from a normal distribution. Group comparisons for categorical measures were performed using the Chi‐square test.We used the two‐sided Survival analysis was conducted to compare the time to the incidence of MCI between exposure groups for three primary outcomes Figure . First, For the present analysis, we used two different survival models to evaluate the impact of hearing loss and hearing aid use on progression from cognitively healthy to MCI, namely, the standard Cox proportional hazards model (as benchmark), adjusted for baseline covariates, and the marginal structural Cox (MSC) model with inverse probability weighting (IPW).P > .05). To account for events that occurred on the same date, we used Efron's approximation, which was previously shown to perform well in the presence of ties.2), normal (≥20.0  and <27.5 kg/m2), or overweight (≥27.5 kg/m2), based on the suggestion that higher cut‐off points may be more appropriate for older adults.P‐values were two‐sided and differences with P < .05 were considered statistically significant.We tested the proportionality of hazards assumption using the Schoenfeld residuals.P < .001), the use of multilevel modeling was supported. The effect of time, exposure allocation  were included as fixed effects. The inclusion of other covariates and time by exposure group interaction was judged against the model fit. Random intercepts and random slopes were modeled for each subject. We confirmed that all models, including the random intercept and the random slope, fitted the data significantly better than models incorporating only fixed effects (P < .001). The Akaike information criterion (AIC) was applied to evaluate the most plausible model in the set of models being tested.P‐values were obtained using Kenward‐Roger approximations for degrees of freedom.Additionally, to assess the impact of hearing impairment and hearing aid usage on cognitive function, we performed longitudinal analyses for Scenarios 1 to 3 using linear mixed effects models with individual CDR‐SB test scores as dependent variables .2.4Sensitivity analysis for unmeasured confounding was performed to study the effect of potential unmeasured covariates on the standardized hazard ratios (HRs), in Scenarios 1 to 3, in IP‐weighted MSC models.33.1We analyzed a total of 4358 participants with no cognitive impairment at baseline. This included 450 10.3%) subjects with hearing impairment and 3908 (89.7%) subjects without hearing impairment. Among 450 participants with hearing impairment, 313 were classified as hearing aid users while 137 were not using hearing aids. Out of 4358 participants, 416 converted to MCI during follow‐up. The mean follow‐up time was 4 years . The ages of the participants ranged from 40 to 80 years, with a median of 68 years (interquartile range: 63 to 73). The baseline characteristics of participants are shown in Table 0.3% subjP <  .001), more educated (P =  .01), and had a higher mean CDR‐SB score (P =  .001) than individuals with normal hearing. A higher proportion of them were females (P <  .001) and suffered from hypercholesterolemia (P =  .001) and heart attack/cardiac arrest (P <  .001). In Scenario 2, non‐users of hearing aids had fewer years of education (P =  .002) and were more likely to suffer from diabetes (P < .001), compared to participants using hearing aids. In Scenario 3, participants with normal hearing were significantly younger (P <  .001), predominantly female (P <  .001), less educated (P <  .001), and had a lower mean CDR‐SB score (P =  .02) than hearing aid users. A lower proportion of them suffered from hypercholesterolemia (P =  .03) and heart attack/cardiac arrest (P <  .001), whereas the percentage of those with diabetes was higher (P =  .03).Given Scenario 1, participants with hearing impairment were significantly older (3.2P  < .001), respectively. The 5‐year IP‐weighted rates of MCI‐free survival were 82.9%  for participants with normal hearing and 62.2%,  for participants with hearing loss. In Scenario 2, the RMST was 9.35 (SE: 0.16) for hearing aid users and 7.61 (SE: 0.31) for non‐users of hearing aids while IP‐weighted event‐free survival at 5 years was 87.5%  and 69.4% , respectively. In Scenario 3, the between‐group difference in RMST was 0.07 years and not statistically significant (P = .62).IP‐adjusted KM survival curves were constructed to compare the timing of incident MCI for different exposure conditions in Scenarios 1 to 3 Figure . The com3.3P < .001; Scenario 1). A significantly reduced risk of MCI was associated with the use of hearing aids . No statistically significant differences in time to incident MCI diagnosis were found between hearing‐impaired individuals that used hearing aids and those with no hearing impairment . HR estimates for all considered covariates are summarized in Table The standard Cox model adjusting for baseline covariates found that, compared to participants with normal hearing, those suffering from hearing loss were at significantly higher risk of incident MCI , compared to those with normal hearing (Scenario 1). In addition, the use of hearing aids was associated with a lower risk of healthy‐to‐MCI conversion . We found no statistically significant differences in risk of incident MCI between participants with normal hearing and hearing‐impaired adults that reported use of hearing aids .All standardized HR estimates were similar to the HRs obtained from the standard Cox model Table . After f3.5Although IP‐weighted MSC models fully account for measured confounders and selection bias, they may still be susceptible to unmeasured confounding bias. Therefore, we conducted sensitivity analysis for unmeasured confounding to further assess the robustness of our results Table . Sensiti3.6P < .001). On average, individuals with hearing impairment tended to have 0.1 points higher CDR‐SB score compared to those without hearing loss (P < .001). Participants with normal hearing also showed less time‐related decline than individuals with hearing loss (P = .004). Accordingly, the annual rate of change in CDR‐SB was 0.012 points higher for individuals with hearing loss. Within Model 2, we found a significant effect of hearing aid status on the CDR‐SB score (P = .01). The CDR‐SB score reported for hearing‐impaired participants using hearing aids was, on average, 0.07 points lower than for non‐users of hearing aids. The mean annual rate of change in CDR‐SB for users and non‐users of hearing aids was 0.04 and 0.08 points, respectively. In Model 3, we observed a significant effect of follow‐up time on the CDR‐SB score (P < .001), with the annual rate of change in CDR‐SB of 0.006 points. Temporal changes in the CDR‐SB score for individuals without hearing loss and hearing‐impaired adults using hearing aids were statistically insignificant (P = .16).In a complementary analysis, we assessed the impact of hearing impairment and hearing aid usage on cognitive function in Scenarios 1 to 3 using linear mixed effects models  with CDR‐SB scores as dependent variables. In Model 1, for every 1‐year increase, CDR‐SB increased by 0.01 (4Our study reveals that hearing impairment is independently associated with accelerated cognitive decline and higher risk of incident MCI. Hearing aid use is linked to lower rates of cognitive decline and reduced risk of incident MCI, with hearing aid users having more than 50% lower risk of MCI, compared to those not using hearing aids. Importantly, we demonstrated that no significant differences in risk of developing MCI and cognitive decline exist between participants experiencing no hearing loss and those diagnosed with hearing impairment using hearing aids. This implies that use of hearing aids may help mitigate cognitive decline associated with hearing loss, offering an actionable strategy to reduce the incidence of MCI. Sensitivity analyses did not affect the results of our primary analysis; hearing loss increases the risk of incident MCI while hearing aid use robustly reduces progression to MCI. The exposure effect of hearing loss and the treatment effect of hearing aids on incident MCI reported using the standard Cox model, persisted after adjusting for time‐dependent and time‐independent factors, and selection bias due to loss to follow‐up in MSC model with IPW and after accounting for unmeasured confounding.Our results are consistent with several observational studies that showed a significant association between hearing loss and accelerated cognitive decline.The potential beneficial treatment effect of hearing aids on cognitive decline observed in our study is consistent with conclusions of previous work.The interpretation of results of our study should be made in light of several limitations. First, the categorization of participants relied solely on self‐reported measures of hearing loss and hearing aid use. Although this may not be a limitation, as indicated in Oosterloo et al.,Although ADRC staff were trained and instructed to report on whether they felt participants’ ability to answer the CDR‐SB questions was impacted by their hearing loss, there is a risk that hearing loss may have confounded cognition results for some participants. Moreover, even though standard criteria and procedures were applied across all ADRCs, there may be some differences in diagnostic definitions and variability in recruitment strategies implemented by each ADRC.Finally, education level and income of ADRC cohort participants are likely higher than the national average and they are predominantly White. Participants who chose to use hearing aids may have differed from those who did not by factors including higher socioeconomic status and education. Therefore, compared to an RCT in which exposure is randomly assigned, the characteristics of participants in our study were unbalanced between exposed and unexposed groups. To address the bias, due to non‐randomized exposure allocation, potential confounding effects of both time‐varying and baseline covariates and selection bias due to drop out, we implemented the IPW approach to fit the MSC model. The IP weighting allowed us to assign exposure/treatment independently of the counterfactual responses and conditional on observed covariates and calculate statistics standardized to a pseudo‐population in which the exposure was independent of the measured confounders. Although the implementation of the IPW‐adjusted MSC models accounted for a large set of measured covariates, selected based on evidence from previous work, there is still a chance that our study may include unmeasured confounding factors that were unintentionally omitted from the analysis. These unmeasured confounders could possibly bias causal inferences in our analysis. To account for the impact of potential unmeasured confounding bias on the associations, we performed the sensitivity analysis for unmeasured confounding. Given that our conclusions remained robust over a wide range of plausible assumptions, thus reducing the number of interpretations of our findings, the causal nature of the observed associations is more defensible.More research is needed to better understand the relationship between hearing impairment and changes in cognitive ability and the role of hearing rehabilitative strategies in mitigating these effects. While waiting for further studies with more objective measurement of audiological deficits facts on the audiological side to complement the cognitive data, the present study provides an important support for links among hearing impairment, hearing aid use, and progression to MCI in cognitively healthy adults. Although causality remains to be determined, we carefully infer that increased access to quality hearing health care might prove an effective preventive intervention to mitigate the impending dementia epidemic.All authors declare that they have no competing interests.Magda Bucholc, Paula L. McClean, Sarah Bauermeister, Stephen Todd contributed to study design. Magda Bucholc did the data analysis and data interpretation. Magda Bucholc drafted the manuscript. Sarah Bauermeister, Daman Kaur, Paula L. McClean, and Stephen Todd critically reviewed the manuscript. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.


The decline of sensory systems during aging has been widely investigated and several papers have correlated the visual, hearing and vestibular systems and the consequences of their functional degeneration. Hearing loss and presbyvestibulopathy have been found to be positively correlated as is with the risk-to-fall.The present study was therefore designed as systematic review (due to PRISMA criteria) which should correlate hearing amplification by hearing aids and/or cochlear implants with balance outcome. However, the literature review  revealed ten paper  with heterogenous patient popiulations and non-uniform outcome measures  so that no quantitative, statistical analysis could be performed.The qualitative analysis oft he identified studies showed that hearing amplification in the elderly improves spatio-temporal orientation (particularly with cochlear implants) and that the process of utilizing auditory information for balance control takes some time , usually some months in cochlear implantees.Hearing and balance function degenerate independently from each other and large interindividual differences require a separate neurotological examination of each patient. However, hearing amplification is most helpful to improve postural stability, particularly in the elderly. Future research should focus on controlled, prospective clinical trials where a standardized test battery covering the audiological and neurotological profile of each elderly patient pre/post prescription of hearing aids and/or cochlear implantation should be followed up (for at least 1 year) so that also the balance improvements and the risk-to-fall can be reliably assessed . The authors conclude therefore that screening of high-frequency HL can be utilized as falls screening procedure since saccular dysfunction makes elderly particularly prone to falls [Presbyvestibulopathy is an age-dependent process of sensory degeneration of the vestibular system which can end up as a clinicially relevant disorder leading to falls. As longitudinal studies of aging have demonstrated, the decline of the sensory systems is inevitable, the most significant correlation can be found  with age (BASE) . The Balto falls , 5. In ato falls , the assto falls  who repoto falls . Anotherto falls .It is therefore the aim of the present review to investigate the impact of diagnosed and treated hearing loss (by hearing aids or hearing implants) on presbyvestibulopathy and, more specifically, the risk-to-fall.A systematic literature review was carried out according to the Preferred Reporting Items for systematic Review and Meta-Analyses (PRISMA) . The seaThe search was conducted in PubMed (MEDLINE) and the Cochrane Library on May 2, 2020. Study bibliographies were searched to locate additional material. The keywords used for the search are given in Table Prospective, controlled studies (PCS) and acute trials were the only identified study types which were included. No animal studies or reports on hearing and balance disorders in children were considered. After removing duplicated titles, abstracts were screened by two reviewers which then both read the full text if considered eligible for this article Fig. . The PRIThe methodological quality assessment of appropriate studies was done by two reviewers, independent from one another. The Cochrane Risk-of-Bias tool (RoB) and the Quality Appraisal Checklist for Case Series  were applied and the studies were assessed with respect to patients ‘ selection, type of intervention, outcome measurement and/or incomplete outcome data.Study characteristics and outcome data were extracted for each study Table . The folThe search identified 2 598 results with the strategy outlined in Table n = 56) was a prospective clinical study (PCS) which used questionnaires to demonstrate the effects of bilateral HA use before and 4 months after the fitting [n = 14, average age 77 yrs). They did not find any significant relationship between improvement in hearing and balance with their test design.Four studies were identified which investigated the influence of hearing aid (HA) use on balance. One study ( fitting . They sh fitting  used a RMcDaniel  used a dn = 22) and age-matched controls without HA (n = 25) on a static posturography platform with respect to static balance . They found that HA improve static balance function by reducing the sway velocity.Negahban et al.  investigOne other study (acute) used gait analysis  to compare 13 bilateral HA users (mean age 83) with 12 bilateral CI users (aged 55), but found no statistically significant differences which might be due to the large epidemiological and age differences between both groups .The review showed four PCS covering the effects of cochlear implantation on balance.n = 10, mean age 55) had come to near-normal values of age-matched healthy controls using a dynamic posturography system. They concluded that the “recovery of auditory information” (by cochlear implantation) could induced the compensatory development of new balance strategies which would explain the improvements.Parietti-Winkler et al.  showed tLouza et al.  performen = 15, mean age 53) vs. bilateral  CI users vs. controls on a dynamic posturography platform using rotating auditory scenes. They found that controls were not affected by those auditory stimuli as well as unilateral CI users (without stereophony), but the rotating sound showed a clear deterioration in the SOT in bilateral CI users. They conclude that the integration of binaural auditory cues in bilateral CI users are important for their balance strategy.Guigou et al.  comparedn = 21, mean age 51) and found at 3 months postop no major differences tot he preop measurements apart from ap sway which was reduced.Wiszomirska et al.  also invThe only acute trial in cochlear implantology that we could idenify was a study by Oikawa et al.  who inven = 216, mean age 60) [It was the aim to screen all relevant databases  for such papers which describe the correlation between hearing amplification (thru HA or CI) and balance outcome. Unfortunately, the few i.e., 10) papers identified were too heterogenous to be used for a quantitative analysis. The type of study design , patient groups and their characteristics and balance assessment tools  were also not enough homogenously to be suited for a meta-analysis. We therefore tried to identify trends and describe mechanisms of interaction between hearing and balance. Two major conclusions can be drawn from most of the publications above: hearing amplification helps to improve spatio-temporal orientation , particularly with CI and that the process of utilizing auditory information for balance control takes some time (due to the underlying neuroplasticity inducing learning and memory formation) so that the acute studies with the hearing systems on/off did not provide very substantial new information. This is in line with cross-sectional studies  which ha0 papers  age 60) . This mi age 60) .While the phenotype of cochlear hearing loss  is neuroanatomically closely correlated to the loss of vestibular and spiral (cochlear) ganglion cells, there is no such correlation to patients with presbycusis . If it cIn essence, hearing and balance have proven, close relationship in the degenerative patterns of ageing, but do decline independently as based on interindividual differences. However, hearing amplification is most helpful in elderly to improve postural stability . Future


Optical Coherence Tomography (OCT) is a powerful instrument for helping clinicians detect and monitor glaucoma. The aim of this study was to provide a detailed mapping of the relationships between visual field (VF) sensitivities and measures of retinal structure provided by a commercial Spectral Domain (SD)-OCT system (RTvue-100 Optovue).Sixty-three eyes of open angle glaucoma patients  were included in this retrospective, observational clinical study. Thickness values for superior and inferior retina, as well as average values, were recorded for the full retina, the outer retina, the ganglion cell complex, and the peripapillary retinal nerve fiber layer (RNFL). RNFL thickness was further evaluated along eight separate sectors . Point-wise correlations were then computed between each of these OCT measures and the visual sensitivities at all VF locations assessed via Humphrey 10-2 and 24-2 perimetry. Lastly, OCT data were fit to VF data to predict glaucoma stage.The relationship between retinal thickness and visual sensitivities reflects the known topography of the retina. Spatial correlation patterns between visual sensitivities and RNFL thickness along different sectors broadly agree with previously hypothesized structure–function maps, yet suggest that structure–function maps still require more precise characterizations. Given these relationships, we find that OCT data can predict glaucoma stage.Ganglion cell complex and RNFL thickness measurements are highlighted as the most promising candidate metrics for glaucoma detection and monitoring. Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and visual field (VF) loss. Optical Coherence Tomography (OCT) is a powerful instrument for helping clinicians to detect and monitor glaucoma onset and progression. However, the diagnostic capacity of OCT data to predict specific spatial patterns of glaucomatous visual loss, particularly in central vision, is unclear. To address this gap in the literature, here we determine the point-wise correlations between VF sensitivities and retinal thickness measurements taken via spectral domain OCT (SD-OCT) in open angle glaucoma patients. Specifically, we measured the thickness of the full retina, the outer retina, and the ganglion cell complex (GCC) at the macula, as well as the thickness of the peripapillary retinal nerve fiber layer (RNFL). We related these retinal thickness measurements to Humphrey 10-2 and 24-2 VF measurements. In particular, both macular GCC thickness and RNFL thickness have been demonstrated to have diagnostic potential for detecting early, moderate, and severe glaucoma . Conversely, peripheral 24-2 visual sensitivities measured in the right eye were more strongly and significantly correlated with visual sensitivities measured in the left eye; mean r = 0.42, 95% confidence interval [0.38–0.46].Figure r = 0.59, p = 0.0010), or across only the superior  or inferior  portions of the retina.Figure r = 0.45, p = 0.020) and the superior  retina, but not for the inferior retina . The thickness of the outer retina  and the inferior  retina, but not for the superior retina . The thickness of the RNFL  or the superior  retina, but not when measured across the inferior  portions of the retina. In addition, Fig. The thickness of the GCC Fig.  was alsoina Fig.  was signNFL Fig.  was signr = 0.61, p = 0.00043 and r = 0.63, p = 0.00038), whereas retinal thickness values measured across the superior retina were most strongly correlated with inferior 10-2 VF sensitivities . This pattern of spatial correlations was also similarly observed in the peripheral VF , retinal thickness values measured across the superior retina were most strongly correlated with inferior 24-2 VF sensitivities .The full thickness of all retinal layers was significantly and positively correlated with both 10-2 and 24-2 VF data , whereas GCC thickness values measured across the superior retina were most strongly correlated with inferior 10-2 VF sensitivities . In the peripheral VF , GCC thickness values measured across the superior retina were most strongly correlated with inferior 24-2 VF sensitivities .The patterns of spatial correlations between GCC thickness and VF data Fig.  were str VF Fig. , GCC retr = −0.47, p = 0.011; r = −0.48, p = 0.012; r = −0.34, p = 0.080). The pattern was similar in the peripheral VF as well .The thickness of the outer retina was generally less strongly (and often inversely) associated with VF sensitivity Fig. . Near thr = 0.42, p = 0.020 and r = 0.48, p = 0.0088), whereas RNFL thickness values measured across the superior retina were most strongly correlated with inferior 10-2 VF sensitivities . In the peripheral VF , RNFL thickness values measured across the superior retina were most strongly correlated with inferior 24-2 VF sensitivities .The patterns of spatial correlations between RNFL thickness and VF data Fig.  were onc VF Fig. , RNFL rer = 0.50, p = 0.0070; r = 0.63, p = 0.00030), RNFL thickness along the temporal upper, superior nasal, nasal upper, and nasal lower sectors significantly correlated with the lower VF sensitivities , while the correlations between VF sensitivities and RNFL thickness along superior temporal and inferior nasal sectors did not reach statistical significance . In the visual periphery , RNFL thickness along the temporal upper, superior temporal, superior nasal, nasal upper and nasal lower sectors significantly correlated with the lower VF sensitivities , and the correlations between VF sensitivities and RNFL thickness along the inferior nasal sector did not reach statistical significance .Figure ery Fig.  RNFL thiF1,21 = 5.23, p = 0.0044, r2 = 0.50) and CPSD  data from OCT parameters. Figure r = 0.68, p = 0.00012, r2 = 0.47). Figure F1,19 = 8.71, p = 8.2 × 10−5, r2 = 0.76) and CPSD  data from OCT parameters. Figure r = 0.87, p = 2.5 × 10−9, r2 = 0.77).Figure RNFL thickness can be assessed at the ONH, in the peripapillary area and in the macula and all have been shown to be good indicators of retinal ganglion cell damage for glaucoma diagnosis , 13. In Hood et al. first showed that macular damage occurs in about 90% of patients with early glaucoma, and macular damage within 10° is increasingly recognized as a common disease feature –17. ThesUsing a Retinal Thickness Analyzer  Zeimer et al. first hypothesized the possibility to detect the loss of ganglion cells analysing the posterior pole . FollowiIn our study, we found that the zones with lower correlations with retinal thickness measurements were located more peripherally in the VF and this could be due to the fact that the peripheral field is more prone to fluctuation or variability. The use of the 10-2 VF perimetry for central VF testing more accurately represents visual function in the macula. The use of 24-2 VF testing could therefore be insufficient to accurately characterize central VF deficits due to its limited spatial sampling. Indeed, the distance between testing locations in the 24-2 perimetry is 6°, whereas testing locations are 2° apart in 10-2 perimetry. While 24-2 perimetry is useful in detecting peripheral glaucomatous damage such as nasal step or arcuate scotomas, 10-2 perimetry is likely more sensitive for the detection of paracentral scotomas. Our results further show that paracentral scotomas are also more likely to be asymmetric across the two eyes compared with peripheral VF defects. This may impact binocular vision and stereoscopic depth perception, and particularly impede fine eye movements in depth and eye-hand coordination –31.Our results further show that GCC and RNFL thickness measurements are more sensitive than outer retina thickness measurements in predicting VF loss. This confirms that in glaucoma the main changes occur in the inner layers of the retina where ganglion cells are present. For both 10-2 and 24-2 perimetry, correlation patters were strongest between OCT measurements of the inferior retina and superior VF sensitivities, and for OCT measurements of the superior retina and inferior VF sensitivities. These correlations could be affected by the selection of the cohort of patients and could be due to the type of damage found. Of course, the more common structural damage is in the infero-temporal disc rim/RNFL outlining the obtained results. When the patterns of spatial correlations between VF sensitivity and RNFL thickness measured along eight separate sectors was analyzed, we further observed significant structure–function correlations for most of the sectors. As in previous studies , 10-2 VFIn conclusion the structure–function maps we obtained were largely consistent with the mappings previously reported. The inferior retina (measured via OCT) was found to be a more vulnerable area and was well correlated to superior central VF test points. Collected data and analyses highlight GCC and RNFL thickness measurements as the most promising candidate metrics for glaucoma detection and monitoring.Structure–function maps with 30-2 visual field have already been published, but less is known on 10-2 visual field.This study shows ganglion cell complex and peripapillary correlations as first step to create a new 10-2 clinical map.