Blood and urine multi-omics analysis of the impact of e-vaping, smoking, and cessation: from exposome to molecular responses.

Cigarette smoking is a major preventable cause of morbidity and mortality. While quitting smoking is the best option, switching from cigarettes to non-combustible alternatives (NCAs) such as e-vapor products is a viable harm reduction approach for smokers who would otherwise continue to smoke. A key challenge for the clinical assessment of NCAs is that self-reported product use can be unreliable, compromising the proper evaluation of their risk reduction potential. In this cross-sectional study of 205 healthy volunteers, we combined comprehensive exposure characterization with in-depth multi-omics profiling to compare effects across four study groups: cigarette smokers (CS), e-vapor users (EV), former smokers (FS), and never smokers (NS). Multi-omics analyses included metabolomics, transcriptomics, DNA methylomics, proteomics, and lipidomics. Comparison of the molecular effects between CS and NS recapitulated several previous observations, such as increased inflammatory markers in CS. Generally, FS and EV demonstrated intermediate molecular effects between the NS and CS groups. Stratification of the FS and EV by combustion exposure markers suggested that this position on the spectrum between CS and NS was partially driven by non-compliance/dual use. Overall, this study highlights the importance of in-depth exposure characterization before biological effect characterization for any NCA assessment study.

The impact of biological clock and sex hormones on the risk of disease.

Molecular clocks are responsible for defining 24-h cycles of behaviour and physiology that are called circadian rhythms. Several structures and tissues are responsible for generating these circadian rhythms and are named circadian clocks. The suprachiasmatic nucleus of the hypothalamus is believed to be the master circadian clock receiving light input via the optic nerve and aligning internal rhythms with environmental cues. Studies using both in vivo and in vitro methodologies have reported the relationship between the molecular clock and sex hormones. The circadian system is directly responsible for controlling the synthesis of sex hormones and this synthesis varies according to the time of day and phase of the estrous cycle. Sex hormones also directly interact with the circadian system to regulate circadian gene expression, adjust biological processes, and even adjust their own synthesis. Several diseases have been linked with alterations in either the sex hormone background or the molecular clock. So, in this chapter we aim to summarize the current understanding of the relationship between the circadian system and sex hormones and their combined role in the onset of several related diseases.

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases.

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.

Hypoparathyroidism, deafness and renal dysplasia syndrome caused by a GATA3 splice site mutation leading to the activation of a cryptic splice site.

The HDR syndrome is a rare autosomal dominant disorder characterised by Hypoparathyroidism, Deafness, and Renal dysplasia, and is caused by inactivating heterozygous germline mutations in the GATA3 gene. We report an 11-year-old girl with HDR syndrome caused by a heterozygous mutation located at the splice acceptor site of exon 5 of the GATA3 gene (NM_001002295.2: c.925-1G>T). Functional studies using a minigene assay showed that this splice site mutation abolished the normal splicing of the GATA3 pre-mRNA and led to the use of a cryptic splice acceptor site, resulting in the loss of the first seven nucleotides (TCTGCAG) of exon 5 in the GATA3 mRNA. These findings increase the understanding of the mechanisms by which GATA3 splicing mutations can cause HDR syndrome.

Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System.

Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn's disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms.

Results and lessons learned from the sbv IMPROVER metagenomics diagnostics for inflammatory bowel disease challenge.

A growing body of evidence links gut microbiota changes with inflammatory bowel disease (IBD), raising the potential benefit of exploiting metagenomics data for non-invasive IBD diagnostics. The sbv IMPROVER metagenomics diagnosis for inflammatory bowel disease challenge investigated computational metagenomics methods for discriminating IBD and nonIBD subjects. Participants in this challenge were given independent training and test metagenomics data from IBD and nonIBD subjects, which could be wither either raw read data (sub-challenge 1, SC1) or processed Taxonomy- and Function-based profiles (sub-challenge 2, SC2). A total of 81 anonymized submissions were received between September 2019 and March 2020. Most participants' predictions performed better than random predictions in classifying IBD versus nonIBD, Ulcerative Colitis (UC) versus nonIBD, and Crohn's Disease (CD) versus nonIBD. However, discrimination between UC and CD remains challenging, with the classification quality similar to the set of random predictions. We analyzed the class prediction accuracy, the metagenomics features by the teams, and computational methods used. These results will be openly shared with the scientific community to help advance IBD research and illustrate the application of a range of computational methodologies for effective metagenomic classification.

An in vitro evaluation of e-vapor products: The contributions of chemical adulteration, concentration, and device power.

Homemade e-liquids and power-adjustable vaping devices may carry higher risks than commercial formulations and fixed-power devices. This study used human macrophage-like and bronchial epithelial (NHBE) cell cultures to investigate toxicity of homemade e-liquids containing propylene glycol and vegetable glycerin (PG/VG), nicotine, vitamin E acetate (VEA), medium-chain fatty acids (MCFAs), phytol, and cannabidiol (CBD). SmallAir™ organotypic epithelial cultures were exposed to aerosols generated at different power settings (10-50 W). Carbonyl levels were measured, and endpoints reflecting epithelial function (ciliary beating frequency [CBF]), integrity (transepithelial electrical resistance [TEER]), and structure (histology) were investigated. Treatment with nicotine or VEA alone or with PG/VG did not impact cell viability. CBD, phytol, and lauric acid caused cytotoxicity in both culture systems and increased lipid-laden macrophages. Exposure of SmallAir™ organotypic cultures to CBD-containing aerosols resulted in tissue injury and loss of CBF and TEER, while PG/VG alone or with nicotine or VEA did not. Aerosols generated with higher power settings had higher carbonyl concentrations. In conclusion, the presence and concentration of certain chemicals and device power may induce cytotoxicity in vitro. These results raise concerns that power-adjustable devices may generate toxic compounds and suggest that toxicity assessments should be conducted for both e-liquid formulations and their aerosols.

Remarkable sex-specific differences at single-cell resolution in neonatal hyperoxic lung injury.

Exposure to supraphysiological concentrations of oxygen (hyperoxia) predisposes to bronchopulmonary dysplasia (BPD), which is characterized by abnormal alveolarization and pulmonary vascular development, in preterm neonates. Neonatal hyperoxia exposure is used to recapitulate the phenotype of human BPD in murine models. Male sex is considered an independent predictor for the development of BPD, but the main mechanisms underlying sexually dimorphic outcomes are unknown. Our objective was to investigate sex-specific and cell-type specific transcriptional changes that drive injury in the neonatal lung exposed to hyperoxia at single-cell resolution and delineate the changes in cell-cell communication networks in the developing lung. We used single-cell RNA sequencing (scRNAseq) to generate transcriptional profiles of >35,000 cells isolated from the lungs of neonatal male and female C57BL/6 mice exposed to 95% [Formula: see text] between PND1-5 (saccular stage of lung development) or normoxia and euthanized at PND7 (alveolar stage of lung development). ScRNAseq identified 22 cell clusters with distinct populations of endothelial, epithelial, mesenchymal, and immune cells. Our data identified that the distal lung vascular endothelium (composed of aerocytes and general capillary endothelial cells) is exquisitely sensitive to hyperoxia exposure with the emergence of an intermediate capillary endothelial population with both general capillaries (gCap) and aerocytes or alveolar capillaries (aCap) markers. We also identified a myeloid-derived suppressor cell population from the lung neutrophils. Sex-specific differences were evident in all lung cell subpopulations but were striking among the lung immune cells. Finally, we identified that the specific intercellular communication networks and the ligand-receptor pairs that are impacted by neonatal hyperoxia exposure.

Systems biology reveals anatabine to be an NRF2 activator.

Anatabine, an alkaloid present in plants of the So lanaceae family (including tobacco and eggplant), has been shown to ameliorate chronic inflammatory conditions in mouse models, such as Alzheimer's disease, Hashimoto's thyroiditis, multiple sclerosis, and intestinal inflammation. However, the mechanisms of action of anatabine remain unclear. To understand the impact of anatabine on cellular systems and identify the molecular pathways that are perturbed, we designed a study to examine the concentration-dependent effects of anatabine on various cell types by using a systems pharmacology approach. The resulting dataset, consisting of measurements of various omics data types at different time points, was analyzed by using multiple computational techniques. To identify concentration-dependent activated pathways, we performed linear modeling followed by gene set enrichment. To predict the functional partners of anatabine and the involved pathways, we harnessed the LINCS L1000 dataset's wealth of information and implemented integer linear programming on directed graphs, respectively. Finally, we experimentally verified our key computational predictions. Using an appropriate luciferase reporter cell system, we were able to demonstrate that anatabine treatment results in NRF2 (nuclear factor-erythroid factor 2-related factor 2) translocation, and our systematic phosphoproteomic assays showed that anatabine treatment results in activation of MAPK signaling. While there are certain areas to be explored in deciphering the exact anti-inflammatory mechanisms of action of anatabine and other NRF2 activators, we believe that anatabine constitutes an interesting molecule for its therapeutic potential in NRF2-related diseases.

MyCTC chip: microfluidic-based drug screen with patient-derived tumour cells from liquid biopsies.

Cancer patients with advanced disease are characterized by intrinsic challenges in predicting drug response patterns, often leading to ineffective treatment. Current clinical practice for treatment decision-making is commonly based on primary or secondary tumour biopsies, yet when disease progression accelerates, tissue biopsies are not performed on a regular basis. It is in this context that liquid biopsies may offer a unique window to uncover key vulnerabilities, providing valuable information about previously underappreciated treatment opportunities. Here, we present MyCTC chip, a novel microfluidic device enabling the isolation, culture and drug susceptibility testing of cancer cells derived from liquid biopsies. Cancer cell capture is achieved through a label-free, antigen-agnostic enrichment method, and it is followed by cultivation in dedicated conditions, allowing on-chip expansion of captured cells. Upon growth, cancer cells are then transferred to drug screen chambers located within the same device, where multiple compounds can be tested simultaneously. We demonstrate MyCTC chip performance by means of spike-in experiments with patient-derived breast circulating tumour cells, enabling >95% capture rates, as well as prospective processing of blood from breast cancer patients and ascites fluid from patients with ovarian, tubal and endometrial cancer, where sensitivity to specific chemotherapeutic agents was identified. Together, we provide evidence that MyCTC chip may be used to identify personalized drug response patterns in patients with advanced metastatic disease and with limited treatment opportunities.

A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.

The majority of pituitary adenomas occur in a sporadic context, and in the absence of known genetic predisposition. Three common variants at the NEBL (rs2359536), PCDH15 (rs10763170) and CDK8 (rs17083838) loci were previously associated with sporadic pituitary adenomas in the Han Chinese population, but these findings have not yet been replicated in any other population. The aim of this case-control study was to assess if these variants are associated with susceptibility to sporadic pituitary adenomas in the Portuguese population. Genotype and allele frequencies were determined in 570 cases and in 546 controls. The CDK8 rs17083838 minor allele (A allele) was significantly associated with sporadic pituitary adenomas, under an additive (odds ratio (OR) 1.73, 95% confidence interval (CI) 1.19-2.50, p = 0.004) and dominant (OR 1.82, 95% CI 1.24-2.68, p = 0.002) inheritance model. The NEBL rs2359536 and PCDH15 rs10763170 variants were not associated with the overall risk for the disease, although a borderline significant association was observed between the PCDH15 rs10763170 minor allele (T allele) and somatotrophinomas (dominant model, OR 1.55, 95% CI 1.02-2.35, p = 0.035). These findings suggest that the CDK8 rs17083838 variant, and possibly the PCDH15 rs10763170 variant, may increase susceptibility to sporadic pituitary adenomas in the Portuguese population.

Disorder of Sex Development Due to 17-Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency: A Case Report and Review of 70 Different HSD17B3 Mutations Reported in 239 Patients.

The 17-beta-hydroxysteroid dehydrogenase type 3 (17-ß-HSD3) enzyme converts androstenedione to testosterone and is encoded by the HSD17B3 gene. Homozygous or compound heterozygous HSD17B3 mutations block the synthesis of testosterone in the fetal testis, resulting in a Disorder of Sex Development (DSD). We describe a child raised as a female in whom the discovery of testes in the inguinal canals led to a genetic study by whole exome sequencing (WES) and to the identification of a compound heterozygous mutation of the HSD17B3 gene (c.608C>T, p.Ala203Val, and c.645A>T, p.Glu215Asp). Furthermore, we review all HSD17B3 mutations published so far in cases of 17-ß-HSD3 deficiency. A total of 70 different HSD17B3 mutations have so far been reported in 239 patients from 187 families. A total of 118 families had homozygous mutations, 63 had compound heterozygous mutations and six had undetermined genotypes. Mutations occurred in all 11 exons and were missense (55%), splice-site (29%), small deletions and insertions (7%), nonsense (5%), and multiple exon deletions and duplications (2%). Several mutations were recurrent and missense mutations at codon 80 and the splice-site mutation c.277+4A>T each represented 17% of all mutated alleles. These findings may be useful to those involved in the clinical management and genetic diagnosis of this disorder.

Prevalence of Mental Health and Social Connection among Patients Seeking Tobacco Dependence Management: A Pilot Study.

INTRODUCTION: with regards to tobacco dependence management, there are certain barriers to successful smoking cessation for patients, such as untreated anxiety and depression. Complicating the impact of mental health morbidities on tobacco dependence may be the significant portion of patients whose mental health issues and limited social connections are undiagnosed and unaddressed. We hypothesize that patients with no prior mental health diagnoses who are treated for tobacco dependence have high rates of undiagnosed mental health morbidities. METHODS: patients were recruited from a tobacco treatment clinic in 2021. Every patient who came for an inaugural visit without a prior diagnosis of mental health disease was screened for depression, anxiety, social isolation and loneliness. Sociodemographic variables were collected. RESULTS: over a 12-month period, 114 patients were seen at the tobacco treatment clinic. Of these 114 patients, 77 (67.5%) did not have a prior diagnosis of a mental health disease. The mean age was 54.3 ± 11.2 years, 52 (67.5%) were females, and 64 (83.1%) were Black/African American. The mean age of starting smoking was 19.3 ± 5.2 years, and 43 (55.8%) had never attempted to quit smoking in the past. With regards to mental health screening, 32 (41.6%) patients had a score of 9 or greater on the Patient Health Questionnaire (PHQ) 9, 59 (76.6%) had a score of 7 or greater on the Generalized Anxiety Disorder (GAD) 7, 67 (87.0%) were identified with social isolation and 70 (90.1%) for loneliness on screening. CONCLUSION: there was a high prevalence of undiagnosed mental health morbidities and social disconnection in patients who were actively smoking and were struggling to achieve smoking cessation. While a larger scale study is necessary to reaffirm these results, screening for mental health morbidities and social disconnection may be warranted in order to provide effective tobacco dependence management.

Toxicological Assessment of Flavor Ingredients in E-Vapor Products.

Many flavor ingredients are often used in potentially reduced-risk tobacco products (such as e-vapor products). Although most are "generally recognized as safe (GRAS)" when used in food, there is limited information available on their long-term health effects when delivered by inhalation. While obtaining route-of-exposure-specific toxicological data on flavor ingredients is critical to product evaluation, the large number of individual flavor ingredients available and their potential combinations render classical toxicological assessment approaches impractical, as they may require years of preclinical investigations and thousands of laboratory animals. Therefore, we propose a pragmatic approach in which flavor ingredients are initially assigned to groups of structurally related compounds (Flavor Groups), from which flavor group representatives (FGR) are then selected and tested individually and as a mixture in vitro and in vivo. The premise is that structurally related compounds would have comparable metabolic and biological activity and that the data generated using FGRs could support the toxicological assessment of other structurally related flavor ingredients of their respective Flavor Groups. This approach is explained in a step-wise manner and exemplified by a case study, along with its strengths, limitations as well as recommendations for further confirmatory testing. Once completed, this FGR approach could significantly reduce the time and resources required for filling the data gap in understanding the health risks of many flavor ingredients while also minimizing the need for laboratory animals.

A Novel FGFR1 Missense Mutation in a Portuguese Family with Congenital Hypogonadotropic Hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a rare reproductive endocrine disorder characterized by complete or partial failure of pubertal development and infertility due to deficiency of the gonadotropin-releasing hormone (GnRH). CHH has a significant clinical heterogeneity and can be caused by mutations in over 30 genes. The aim of this study was to investigate the genetic defect in two siblings with CHH. A woman with CHH associated with anosmia and her brother with normosmic CHH were investigated by whole exome sequencing. The genetic studies revealed a novel heterozygous missense mutation in the Fibroblast Growth Factor Receptor 1 (FGFR1) gene (NM_023110.3: c.242T>C, p.Ile81Thr) in the affected siblings and in their unaffected father. The mutation affected a conserved amino acid within the first Ig-like domain (D1) of the protein, was predicted to be pathogenic by structure and sequence-based prediction methods, and was absent in ethnically matched controls. These were consistent with a critical role for the identified missense mutation in the activity of the FGFR1 protein. In conclusion, our identification of a novel missense mutation of the FGFR1 gene associated with a variable expression and incomplete penetrance of CHH extends the known mutational spectrum of this gene and may contribute to the understanding of the pathogenesis of CHH.

O Impacto da COVID-19 no Diagnóstico de Doenças Cardíacas na América Latina Uma Subanálise do INCAPS COVID / The Impact of COVID-19 on Diagnosis of Heart Disease in Latin America an INCAPS COVID Sub-analysis

Resumo Fundamento A pandemia de COVID-19 interferiu na prestação de atendimento a doenças cardiovasculares na América Latina. No entanto, o efeito da pandemia nos volumes de procedimentos cardíacos diagnósticos ainda não foi quantificado. Objetivo Avaliar (1) o impacto de COVID-19 nos volumes de diagnóstico cardíaco na América Latina e (2) determinar sua relação com a incidência de casos de COVID-19 e as medidas de distanciamento social. Métodos A International Atomic Energy Agency realizou uma pesquisa mundial avaliando mudanças nos volumes diagnósticos cardíacos decorrentes da COVID-19. Foram obtidos os volumes diagnósticos cardíacos dos locais participantes para março e abril de 2020 e comparados com março de 2019. Foram coletados dados de distanciamento social a partir dos Relatórios de mobilidade da comunidade de Google e a incidência de COVID-19 por país a partir de Our World in Data. Resultados Foram realizadas pesquisas em 194 centros que realizam procedimentos diagnósticos cardíacos, em 19 países da América Latina. Em comparação com o mês de março de 2019, os volumes dos procedimentos diagnósticos cardíacos diminuíram 36% em março de 2020 e 82% em abril de 2020.As maiores reduções ocorreram em relação aos testes de estresse ecocardiográfico (91%), testes ergométricos de esteira (88%) e escore de cálcio por tomografia computadorizada (87%), com pequenas variações entre as sub-regiões da América Latina. As mudanças em padrões de distanciamento social (p < 0,001) estavam mais fortemente associadas com a redução do volume do que a incidência de COVID-19 (p = 0,003). Conclusões A COVID-19 foi associada a uma redução significativa de procedimentos diagnósticos cardíacos na América Latina, a qual foi mais relacionada ao distanciamento social do que ao aumento da incidência da COVID-19. São necessários melhor equilíbrio e timing de medidas de distanciamento social e planejamento para manter o acesso ao atendimento médico durante um surto pandêmico, especialmente em regiões com alta mortalidade cardiovascular.

Abstract Background The COVID-19 pandemic has disrupted the delivery of care for cardiovascular diseases in Latin America. However, the effect of the pandemic on the cardiac diagnostic procedure volumes has not been quantified. Objective To assess (1) the impact of COVID-19 on cardiac diagnostic volumes in Latin America and (2) determine its relationship with COVID-19 case incidence and social distancing measures. Methods The International Atomic Energy Agency conducted a worldwide survey assessing changes in cardiac diagnostic volumes resulting from COVID-19. Cardiac diagnostic volumes were obtained from participating sites for March and April 2020 and compared to March 2019. Social distancing data were collected from Google COVID-19 community mobility reports and COVID-19 incidence per country from the Our World in Data. Results Surveys were conducted in 194 centers performing cardiac diagnostic procedures, in 19 countries in Latin America. Procedure volumes decreased 36% from March 2019 to March 2020, and 82% from March 2019 to April 2020. The greatest decreases occurred in echocardiogram stress tests (91%), exercise treadmill tests (88%), and computed tomography calcium scores (87%), with slight variations between sub-regions of Latin America. Changes in social distancing patterns (p < 0.001) were more strongly associated with volume reduction than COVID-19 incidence (p = 0.003). Conclusions COVID-19 was associated with a significant reduction in cardiac diagnostic procedures in Latin America, which was more related to social distancing than to the COVID-19 incidence. Better balance and timing of social distancing measures and planning to maintain access to medical care is warranted during a pandemic surge, especially in regions with high cardiovascular mortality.

Impact of aerosols on liver xenobiotic metabolism: A comparison of two methods of exposure.

Assessment of aerosols effects on liver CYP function generally involves aqueous fractions (AF). Although easy and efficient, this method has not been optimized recently or comparatively assessed against other aerosol exposure methods. Here, we comparatively evaluated the effects of the AFs of cigarette smoke (CS) and Tobacco Heating System (THS) aerosols on CYP activity in liver spheroids. We then used these data to develop a physiological aerosol exposure system combining a multi-organs-on-a-chip, 3D lung tissues, liver spheroids, and a direct aerosol exposure system. Liver spheroids incubated with CS AF showed a dose-dependent increase in CYP1A1/1B1, CYP1A2, and CYP2B6 activity and a dose-dependent decrease in CYP2C9, CYP2D6, and CYP3A4 activity relative to untreated tissues. In our physiological exposure system, repeated CS exposure of the bronchial tissues also caused CYP1A1/1B1 and CYP1A2 induction in the bronchial tissues and liver spheroids; but the spheroids showed an increase in CYP3A4 activity and no effect on CYP2C9 or CYP2D6 activity relative to air-exposed tissues, which resembles the results reported in smokers. THS aerosol did not affect CYP activity in bronchial or liver tissues, even at 4 times higher concentrations than CS. In conclusion, our system allows us to physiologically test the effects of CS or other aerosols on lung and liver tissues cultured in the same chip circuit, thus delivering more in vivo like data.

Bone-anchored hearing system, contralateral routing of signals hearing aid or cochlear implant: what is best in single-sided deafness?

PURPOSE: The aim of the study was to compare long-term results after 1 year in patients with single-sided deafness (SSD) who were fitted with different hearing aids. The participants tested contralateral routing of signals (CROS) hearing aids and bone-anchored hearing systems (BAHS). They were also informed about the possibility of a cochlear implant (CI) and chose one of the three devices. We also investigated which factors influenced the choice of device. METHODS: Prospective study with 89 SSD participants who were divided into three groups by choosing BAHS, CROS, or CI. All participants received test batteries with both objective hearing tests (speech perception in noise and sound localisation) and subjective questionnaires. RESULTS: 16 participants opted for BAHS-, 13 for CROS- and 30 for CI-treatment. The greater the subjective impairment caused by SSD, the more likely patients were to opt for surgical treatment (BAHS or CI). The best results in terms of speech perception in noise (especially when sound reaches the deaf ear and noise the hearing ear), sound localization, and subjective results were achieved with CI. CONCLUSION: The best results regarding the therapy of SSD are achieved with a CI, followed by BAHS. This was evident both in objective tests and in the subjective questionnaires. Nevertheless, an individual decision is required in each case as to which SSD therapy option is best for the patient. Above all, the patient's subjective impairment and expectations should be included in the decision-making process.