"Close to My Community": A Qualitative Study of Community Health Worker-Supported Teleaudiology Hearing Aid Services.

OBJECTIVES: Given well-documented disparities in rural and minority communities, alternative service delivery models that help improve access to hearing care are needed. This article reports on a study of older Latino adults with hearing loss who received hearing aid services with Community Health Workers (CHWs) providing support via teleaudiology. The present study used qualitative data to explore perceptions of this novel service delivery model. DESIGN: Participants completed semistructured interviews related to their experiences in the intervention approximately 17 weeks after the hearing aid fitting appointment. Two coders independently coded the data, using an iterative deductive and inductive thematic analysis approach. Inter-rater reliability was good (κ = 0.80). RESULTS: Of the 28 participants, 19 were interviewed (CHW group: n = 9, 8 females; non-CHW group: n = 10, 9 females). Both groups of participants reported experiencing barriers in access to care and reported positive experiences with teleaudiology and with hearing aids as part of the trial. CHW group participants reported interactions with patient-site facilitators that were indicative of patient-centeredness. CONCLUSIONS: Results demonstrate the feasibility and potential effectiveness of trained CHWs as patient-site facilitators in teleaudiology-delivered hearing aid services for adults.

Occupational Lead Exposure Ototoxicity Evaluated With Distortion-Product Otoacoustic Emissions.

OBJECTIVES: To evaluate the extent of hearing loss among pottery workers in Mexico exposed to lead. DESIGN: The authors conducted a cross-sectional study including 315 adult pottery workers. Auditory function was evaluated by air conduction pure-tone audiometry (pure-tone average) and distortion-product otoacoustic emission (DPOAE) levels (amplitude and signal-to-noise ratio). Lead exposure was assessed with a single blood sample test and classified as low, medium, and high according to blood lead tertiles. Logistic regression models were calculated for the association between blood lead levels, pure-tone average, and DPOAE records. RESULTS: Median (25th-75th) blood lead levels were 14 µg/dL (7.5-22.6 µg/dL). The audiometric pattern and DPOAE records were similar across blood lead levels groups in all frequencies, and no statistically significant differences were found. Adjusted logistic regression models showed no increase in the odds for hearing thresholds >25 dB (HL) and DPOAE absence associated with blood lead levels, and no dose-response pattern was observed ( p > 0.05). CONCLUSIONS: Given the results from this cross-sectional study, no association was found between blood lead levels and hearing loss assessed with DPOAE. Future longitudinal work should consider chronic lead exposure estimates among underrepresented populations, which can potentially inform safer work practices to minimize the risk of ototoxicity.

Associations Between Traumatic Brain Injury and Severity of Tinnitus-Related Functional Impairment Among US Military Veterans: A National, Population-Based Study.

OBJECTIVE: To describe associations between a history of traumatic brain injury (TBI) and the severity of tinnitus-related functional impairment among a national, stratified random sample of veterans diagnosed with tinnitus by the Department of Veterans Affairs (VA) healthcare system. SETTING: A multimodal (mailed and internet) survey administered in 2018. Participants: VA healthcare-using veterans diagnosed with tinnitus; veterans with comorbid TBI diagnosis were oversampled. DESIGN: A population-based survey. MAIN MEASURES: TBI history was assessed using International Classification of Diseases (ICD) diagnosis codes in veterans' VA electronic health records. The severity of participants' overall tinnitus-related functional impairment was measured using the Tinnitus Functional Index. Population prevalence and 95% confidence intervals (CIs) were estimated using inverse probability weights accounting for sample stratification and survey nonresponse. Veterans' relative risk ratios of very severe or moderate/severe tinnitus-related functional impairment, versus none/mild impairment, were estimated by TBI history using bivariable and multivariable multinomial logistic regression. RESULTS: The population prevalence of TBI was 5.6% (95% CI: 4.8-6.4) among veterans diagnosed with tinnitus. Veterans with a TBI diagnosis, compared with those without a TBI diagnosis, had 3.6 times greater likelihood of rating their tinnitus-related impairment as very severe (95% CI: 2.1-6.3), and 1.5 times greater likelihood of rating their impairment as moderate/severe (95% CI: 1.0-2.4), versus none/mild. CONCLUSIONS: These findings suggest an important role of TBI in the severity of tinnitus-related functional impairment among veterans. This knowledge can help inform the integration of tinnitus management services into the care received by veterans with TBI.

Community Health Workers as Patient-Site Facilitators in Adult Hearing Aid Services via Synchronous Teleaudiology: Feasibility Results from the Conexiones Randomized Controlled Trial.

OBJECTIVES: The purpose of this study was to investigate the feasibility of Community Health Workers (CHWs) as patient-site facilitators in teleaudiology-facilitated hearing aid services to improve hearing aid rehabilitation outcomes for older Hispanic/Latino adults in a medically underserved, rural, US-Mexico border community. DESIGN: A total of 28 adults (aged 55 to 89) with bilateral hearing loss participated in this study. Individuals were randomized to one of two teleaudiology intervention arms that differed at the level of the patient-site facilitator. Participants in the experimental group were assisted locally by trained CHW facilitators. Participants in the control group were assisted locally by trained university student facilitators. Synchronous (real-time) teleaudiology hearing aid services took place with participants located at a rural community health center and the clinician located a university 70 miles away. The results of this feasibility study are presented within the reach, effectiveness, adoption, implementation fidelity, and maintenance implementation framework. RESULTS: Regarding reach, the participants in this study population are historically under-represented in research (primarily low-income Hispanic/Latino older adults). A total of 57 individuals were recruited, 47 were consented and assessed for eligibility and 28 individuals met inclusion criteria and were randomized. The average age of participants was 73.9 years, (range: 55 to 89 years) and most individuals were female (75%). Most participants (86%) reported having incomes less than $20,000 annually. Effectiveness results (via the Self Efficacy for Situational Communication Management Questionnaire) showed that both groups (CHW and control) significantly improved listening self-efficacy from pre-fitting baseline and no difference between groups was observed. Regarding datalogging, at the short-term follow-up, participants in the CHW group wore their hearing aids for more hours/day on average compared with participants in the control group. Implementation fidelity was high for both groups. Long-term maintenance of CHW-supported teleaudiology appears feasible given that training and institutional support is in place. CONCLUSIONS: Teleaudiology-delivered hearing aid services were feasible when facilitated locally by trained CHWs. Future efficacy and effectiveness research is warranted with CHWs and teleaudiology, potentially leading to a significant reduction in barriers for rural and medically under-resourced communities.

Development and validation of a Spanish-language spatial release from masking task in a Mexican population.

This study validates a new Spanish-language version of the Coordinate Response Measure (CRM) corpus using a well-established measure of spatial release from masking (SRM). Participants were 96 Spanish-speaking young adults without hearing complaints in Mexico City. To present the Spanish-language SRM test, we created new recordings of the CRM with Spanish-language Translations and updated the freely available app (PART; https://ucrbraingamecenter.github.io/PART_Utilities/) to present materials in Spanish. In addition to SRM, we collected baseline data on a battery of non-speech auditory assessments, including detection of frequency modulations, temporal gaps, and modulated broadband noise in the temporal, spectral, and spectrotemporal domains. Data demonstrate that the newly developed speech and non-speech tasks show similar reliability to an earlier report in English-speaking populations. This study demonstrates an approach by which auditory assessment for clinical and basic research can be extended to Spanish-speaking populations for whom testing platforms are not currently available.

Blood Metabolite Profiling of Antarctic Expedition Members: An 1H NMR Spectroscopy-Based Study.

Serum samples from eight participants during the XV winter-over at Concordia base (Antarctic expedition) collected at defined time points, including predeparture, constituted the key substrates for a specific metabolomics study. To ascertain acute changes and chronic adaptation to hypoxia, the metabolic profiles of the serum samples were analyzed using NMR spectroscopy, with principal components analysis (PCA) followed by partial least squares and orthogonal partial least squares discriminant analyses (PLS-DA and OPLS-DA) used as supervised classification methods. Multivariate data analyses clearly highlighted an adaptation period characterized by an increase in the levels of circulating glutamine and lipids, mobilized to supply the body energy needs. At the same time, a reduction in the circulating levels of glutamate and N-acetyl glycoproteins, stress condition indicators, and proinflammatory markers were also found in the NMR data investigation. Subsequent pathway analysis showed possible perturbations in metabolic processes, potentially related to the physiological adaptation, predominantly found by comparing the baseline (at sea level, before mission onset), the base arrival, and the mission ending collected values.

Modulation of the Circulating Extracellular Vesicles in Response to Different Exercise Regimens and Study of Their Inflammatory Effects.

Exercise-released extracellular vesicles (EVs) are emerging as a novel class of exerkines that promotes systemic beneficial effects. However, slight differences in the applied exercise protocols in terms of mode, intensity and duration, as well as the need for standardized protocols for EV isolation, make the comparison of the studies in the literature extremely difficult. This work aims to investigate the EV amount and EV-associated miRNAs released in circulation in response to different physical exercise regimens. Healthy individuals were subjected to different exercise protocols: acute aerobic exercise (AAE) and training (AT), acute maximal aerobic exercise (AMAE) and altitude aerobic training (AAT). We found a tendency for total EVs to increase in the sedentary condition compared to trained participants following AAE. Moreover, the cytofluorimetric analysis showed an increase in CD81+/SGCA+/CD45- EVs in response to AAE. Although a single bout of moderate/maximal exercise did not impact the total EV number, EV-miRNA levels were affected as a result. In detail, EV-associated miR-206, miR-133b and miR-146a were upregulated following AAE, and this trend appeared intensity-dependent. Finally, THP-1 macrophage treatment with exercise-derived EVs induced an increase of the mRNAs encoding for IL-1ß, IL-6 and CD163 using baseline and immediately post-exercise EVs. Still, 1 h post-exercise EVs failed to stimulate a pro-inflammatory program. In conclusion, the reported data provide a better understanding of the release of circulating EVs and their role as mediators of the inflammatory processes associated with exercise.

Community-Based Participatory Research and Human-Centered Design Principles to Advance Hearing Health Equity.

OBJECTIVES: Inclusive and equitable research is an ethical imperative. Community-based participatory research (CBPR) as well as human-centered design are approaches that center partnership between community members and academic researchers. Together, academic-community research teams iteratively study community priorities, collaboratively develop ethical study designs, and co-create innovations that are accessible and meaningful to the community partners while advancing science. The foundation of the CBPR approach is reliant on its core principles of equity, colearning, shared power in decision-making, reciprocity, and mutual benefit. While the CBPR approach has been used extensively in public health and other areas of healthcare research, the approach is relatively new to audiology, otolaryngology, and hearing health research. The purpose of the present article is to advance an understanding of the CBPR approach, along with principles from human-centered design, in the context of research aimed to advance equity and access in hearing healthcare. DESIGN: The literature is reviewed to provide an introduction for auditory scientists to the CBPR approach and human-centered design, including discussion of the underlying principles of CBPR and where it fits along a community-engaged continuum, theoretical and evaluation frameworks, as well as applications within auditory research. RESULTS: Recent applications of CBPR have been framed broadly within the theoretical positions of the socioecological model for a systems-level approach to community-engaged research and the Health Services Utilization model within health services and disparities research using CBPR. Utilizing human-centered design strategies can work in tandem with a CBPR approach to engage a wide range of people in the research process and move toward the development of innovative yet feasible solutions. CONCLUSIONS: Leveraging the principles of CBPR is an intricate and dynamic process, may not be a fit for some topics, some researchers' skillsets, and may be beyond some projects' resources. When implemented skillfully and authentically, CBPR can be of benefit by elevating and empowering community voices and cultural perspectives historically marginalized in society and underrepresented within research. With a focus on health equity, this review of CBPR in the study of hearing healthcare emphasizes how this approach to research can help to advance inclusion, diversity, and access to innovation.

Telehealth solutions for assessing auditory outcomes related to noise and ototoxic exposures in clinic and research.

Nearly 1.5 billion people globally have some decline in hearing ability throughout their lifetime. Many causes for hearing loss are preventable, such as that from exposure to noise and chemicals. According to the World Health Organization, nearly 50% of individuals 12-25 years old are at risk of hearing loss due to recreational noise exposure. In the occupational setting, an estimated 16% of disabling hearing loss is related to occupational noise exposure, highest in developing countries. Ototoxicity is another cause of acquired hearing loss. Audiologic assessment is essential for monitoring hearing health and for the diagnosis and management of hearing loss and related disorders (e.g., tinnitus). However, 44% of the world's population is considered rural and, consequently, lacks access to quality hearing healthcare. Therefore, serving individuals living in rural and under-resourced areas requires creative solutions. Conducting hearing assessments via telehealth is one such solution. Telehealth can be used in a variety of contexts, including noise and ototoxic exposure monitoring, field testing in rural and low-resource settings, and evaluating auditory outcomes in large-scale clinical trials. This overview summarizes current telehealth applications and practices for the audiometric assessment, identification, and monitoring of hearing loss.

Feasibility of community health workers as teleaudiology patient-site facilitators: a multilevel training study.

OBJECTIVE: We evaluated the feasibility of a multi-level teleaudiology patient-site facilitator training program for Community Health Workers (CHWs) at a partnering health centre in southern Arizona. DESIGN: Three levels were offered: Introductory, with basic information on hearing loss and teleaudiology; Intermediate, on technology, team roles, and access issues; and Facilitator, on further knowledge and hands-on skills to serve as patient-site facilitators in synchronous hearing aid service delivery. Six domains of feasibility were addressed using a mixed-methods design. Quantitative data included survey responses and observation of hands-on skills. Qualitative data included field notes from group discussion and open-ended survey questions, and were analysed using CHW core competencies. STUDY SAMPLE: Twelve CHWs participated in the introductory training, ten moved on to intermediate, and three continued to the facilitator. RESULTS: Quantitative outcomes indicated that the trainings were feasible according to each of the six domains. CHWs in the facilitator training passed the practical hands-on skill assessment. Qualitative analyses revealed CHWs comments addressed eight of the ten possible CHW core competencies, and focussed on service coordination/navigation, and capacity building. CONCLUSIONS: Teleaudiology trainings for CHWs were feasible, increasing service capacity for a potential pathway to improve access to hearing health care in low-resource areas.

1H-NMR Profiling Shows as Specific Constituents Strongly Affect the International EVOO Blends Characteristics: The Case of the Italian Oil.

Considering the growing number of extra virgin olive oil (EVOO) producers in the world, knowing the influence of olive oils with different geographical origins on the characteristics of the final blend becomes an interesting goal. The present work is focused on commercial organic EVOO blends obtained by mixing multiple oils from different geographical origins. These blends have been studied by 1H-NMR spectroscopy supported by multivariate statistical analysis. Specific characteristics of commercial organic EVOO blends originated by mixing oils from Italy, Tunisia, Portugal, Spain, and Greece were found to be associated with the increasing content of the Italian component. A linear progression of the metabolic profile defined characteristics for the analysed samples-up to a plateau level-was found in relation to the content of the main constituent of the Italian oil, the monocultivar Coratina. The Italian constituent percentage appears to be correlated with the fatty acids (oleic) and the polyphenols (tyrosol, hydroxytyrosol, and derivatives) content as major and minor components respectively. These results, which highlight important economic aspects, also show the utility of 1H-NMR associated with chemometric analysis as a powerful tool in this field. Mixing oils of different national origins, to obtain blends with specific characteristics, could be profitably controlled by this methodology.

Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine.

A 1H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel nicotinamide derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC50 value, were investigated, with respect to the controls (K), by the 1H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or S-adenosylmethionine (SAM) limitation.

1H NMR Metabolic Profile of Scyphomedusa Rhizostoma pulmo (Scyphozoa, Cnidaria) in Female Gonads and Somatic Tissues: Preliminary Results.

The Mediterranean basin is one of the regions heavily affected by jellyfish bloom phenomena, mainly due to the presence of scyphozoans, such as Rhizostoma pulmo. The jellyfish have few natural predators, and their bodies represent an organic-rich substrate that can support rapid bacterial growth with great impact on the structure of marine food webs. In Asiatic countries, jellyfish are widely studied for their health benefits, but their nutritional and nutraceutical values still remain poorly characterized. In this study, the differences in the 1H NMR spectroscopy metabolic profiles of R. pulmo female gonads and body fractions (including umbrella and oral arms), in different sampling periods, were studied. For each body compartment both lipid and aqueous extracts were characterized and their 1H NMR metabolic profiles subjected to multivariate analysis. From a statistical analysis of the extracts, a higher contents of ω-3 polyunsaturated fatty acids (PUFAs), amino acid and osmolytes (homarine, betaine, taurine) with important roles in marine invertebrates were observed in female gonads, whereas umbrella and oral arms showed similar metabolic profiles. These results support a sustainable exploitation of the jellyfish for the extraction of bioactive compounds useful in nutraceutical, nutricosmetics, and functional food fields.

Screening of Chaetomorpha linum Lipidic Extract as A New Potential Source of Bioactive Compounds.

Recent studies have shown that marine algae represent a great source of natural compounds with several properties. The lipidic extract of the seaweed Chaetomorpha linum (Chlorophyta, Cladophorales), one of the dominant species in the Mar Piccolo of Taranto (Mediterranean, Ionian Sea), revealed an antibacterial activity against Vibrio ordalii and Vibrio vulnificus, common pathogens in aquaculture, suggesting its potential employment to control fish and shellfish diseases due to vibriosis and to reduce the public health hazards related to antibiotic use in aquaculture. This extract showed also an antioxidant activity, corresponding to 170.960 ± 16. mmol Trolox equivalent/g (oxygen radical absorbance capacity assay-ORAC) and to 30.554 ± 2.30 mmol Trolox equivalent/g (Trolox equivalent antioxidant capacity assay-TEAC). The chemical characterization of the extract, performed by 1D and 2D NMR spectroscopy, highlighted the presence of free, saturated (SAFAs), unsaturated (UFAs) and polyunsaturated (PUFAs) fatty acids. The high content of ω-6 and ω-3 PUFAs confirmed also by gas chromatography indicates the potentiality of this algal species in the production of fortified food. The antibacterial activity seems related to the presence of linolenic acid present at high density, while the antioxidant activity could be likely ascribable to molecules such as carotenoids and chlorophylls (characterized also by thin-layer chromatography), known for this property. The presence of polyhydroxybutyrate, a biopolymer with potentiality in the field of biodegradable bioplastics was also detected. The exploitation of C. linum for a future biotechnological application is also encouraged by the results from a first attempt of cultivating this species in an integrated multi-trophic aquaculture (IMTA) system.

Qualitative research methods to investigate communication within a group aural rehabilitation intervention.

Objective: Aural Rehabilitation (AR) aims to minimise negative effects of hearing loss. However, there has been limited study of the lived experience of clients receiving Aural Rehabilitation services, particularly for disparity populations. The purpose of this study is to demonstrate the use of an innovative qualitative approach to investigating communication in an AR setting among Hispanic/Latino older adult dyads. Design: We developed a qualitative phenomenology approach using observation methods to document and analyse how individuals experience living with acquired hearing loss within group AR. Trained observers collected systematic, detailed notes on observations of participants over the course of a 5-week community-based AR intervention. In partnership with audiologists, Community Health Workers facilitated the intervention, which focussed on decreasing negative communication impacts of hearing loss for families. Audiometric data and subjective hearing disability results, using the HHIE-S Spanish version, are presented as additional context for observation outcomes. Study sample: Participants were older Hispanic/Latino adults with hearing loss and their frequent communication partners (five dyads). Results: Four themes related to the experience of communication emerged among dyads in the intervention: (i) emotions related to hearing loss (ii) communication dynamics, (iii) self-management of hearing loss, and (iv) hearing health advocacy. Conclusions: A mixed methods approach that includes group observation would contribute substantially to comprehensively evaluating group AR interventions.

NMR-Based Metabolomics in Metal-Based Drug Research.

Thanks to recent advances in analytical technologies and statistical capabilities, the application field of metabolomics has increased significantly. Currently, this approach is used to investigate biological substrates looking for metabolic profile alterations, diseases markers, and drug effects. In particular, NMR spectroscopy has shown great potential as a detection technique, mainly for the ability to detect multiple (10s to 100s) metabolites at once without separation. Only in recent years has the NMR-based metabolomic approach been extended to investigate the cell metabolic alterations induced by metal-based antitumor drug administration. As expected, these studies are mainly focused on platinum complexes, but some palladium and ruthenium compounds are also under investigation. The use of a metabolomics approach was very effective in assessing tumor response to drugs and providing insights into the mechanism of action and resistance. Therefore, metabolomics may open new perspectives into the development of metal-based drugs. In particular, it has been shown that NMR-based, in vitro metabolomics is a powerful tool for detecting variations of the cell metabolites induced by the metal drug exposure, thus offering also the possibility of identifying specific markers for in vivo monitoring of tumor responsiveness to anticancer treatments.

¹H NMR Spectroscopy and MVA to Evaluate the Effects of Caulerpin-Based Diet on Diplodus sargus Lipid Profiles.

The biological invasion of the green algae Caulerpa cylindracea represents a serious scientific and public issue in the Mediterranean Sea, essentially due to strong modifications both to habitat structure and native benthic communities. Although alterations in health status and changes in flesh quality of some marine species (dietary exposed to C. cylindracea) have been observed, no studies on cause-effect relationships have been carried out. Here, for the first time, through a controlled feeding experiment followed by ¹H NMR Spectroscopy and multivariate analysis (PCA, OPLS-DA), we showed that caulerpin taken with diet is directly responsible of changes observed in metabolic profile of fish flesh, including alteration of lipid metabolism, in particular with a reduction of ω3 PUFA content. The potential of caulerpin to directly modulate lipid metabolism opens up new questions about causal mechanism triggered by algal metabolite also in view of a possible exploitation in the nutraceutical/medical field.

The Jellyfish Rhizostoma pulmo (Cnidaria): Biochemical Composition of Ovaries and Antibacterial Lysozyme-like Activity of the Oocyte Lysate.

Jellyfish outbreaks in marine coastal areas represent an emergent problem worldwide, with negative consequences on human activities and ecosystem functioning. However, potential positive effects of jellyfish biomass proliferation may be envisaged as a natural source of bioactive compounds of pharmaceutical interest. We investigated the biochemical composition of mature female gonads and lysozyme antibacterial activity of oocytes in the Mediterranean barrel jellyfish Rhizostoma pulmo. Chemical characterization was performed by means of multinuclear and multidimensional NMR spectroscopy. The ovaries of R. pulmo were mainly composed of water (93.7 ± 1.9% of wet weight), with organic matter (OM) and dry weight made respectively of proteins (761.76 ± 25.11 µg mg-1 and 45.7 ± 1.5%), lipids (192.17 ± 10.56 µg mg-1 and 9.6 ± 0.6%), and carbohydrates (59.66 ± 2.72 µg mg-1 and 3.7 ± 0.3%). The aqueous extract of R. pulmo gonads contained free amino acids, organic acids, and derivatives; the lipid extract was composed of triglycerides (TG), polyunsaturated fatty acids (PUFAs), diunsaturated fatty acids (DUFAs), monounsaturated fatty acids (MUFAs), saturated fatty acids (SFAs), and minor components such as sterols and phospholipids. The R. pulmo oocyte lysate exhibited an antibacterial lysozyme-like activity (mean diameter of lysis of 9.33 ± 0.32 mm corresponding to 1.21 mg/mL of hen egg-white lysozyme). The occurrence of defense molecules is a crucial mechanism to grant healthy development of mature eggs and fertilized embryos (and the reproductive success of the species) by preventing marine bacterial overgrowth. As a corollary, these results call for future investigations for an exploitation of R. pulmo biomasses as a resource of bioactive metabolites of biotechnological importance including pharmaceuticals and nutrition.

Response of Cisplatin Resistant Skov-3 Cells to [Pt(O,O'-Acac)(γ-Acac)(DMS)] Treatment Revealed by a Metabolomic ¹H-NMR Study.

The novel [Pt(O,O'-acac)(γ-acac)(DMS)], Ptac2S, Pt(II) complex has recently gained increasing attention as a potential anticancer agent for its pharmacological activity shown in different tumor cell lines, studied both in vitro and in vivo. The mechanism of action of Ptac2S, operating on non-genomic targets, is known to be very different from that of cis-[PtCl2(NH3)2], cisplatin, targeting nucleic acids. In this work, we evaluated the cytotoxicity of Ptac2S on the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells, by the MTT assay. A ¹H-NMR metabolomic approach coupled with multivariate statistical analysis was used for the first time for Ptac2S to figure out the biological mechanisms of action of the complex. The metabolic variations of intracellular metabolites and the composition of the corresponding extracellular culture media were compared to those of cisplatin (cells were treated at the IC50 doses of both drugs). The reported comparative metabolomic analysis revealed a very different metabolic profile between Ptac2S and cisplatin treated samples, thus confirming the different mechanism of action of Ptac2S also in the Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells line. In particular, higher levels of pyruvate were observed in Ptac2S treated, with respect to cisplatin treated, cells (in both aqueous and culture media). In addition, a very different lipid expression resulted after the exposure to the two drugs (Ptac2S and cisplatin). These results suggest a possible explanation for the Ptac2S ability to circumvent cisplatin resistance in SKOV-3 cells.

1H NMR Spectroscopy and MVA Analysis of Diplodus sargus Eating the Exotic Pest Caulerpa cylindracea.

The green alga Caulerpa cylindracea is a non-autochthonous and invasive species that is severely affecting the native communities in the Mediterranean Sea. Recent researches show that the native edible fish Diplodus sargus actively feeds on this alga and cellular and physiological alterations have been related to the novel alimentary habits. The complex effects of such a trophic exposure to the invasive pest are still poorly understood. Here we report on the metabolic profiles of plasma from D. sargus individuals exposed to C. cylindracea along the southern Italian coast, using 1H NMR spectroscopy and multivariate analysis (Principal Component Analysis, PCA, Orthogonal Partial Least Square, PLS, and Orthogonal Partial Least Square Discriminant Analysis, OPLS-DA). Fish were sampled in two seasonal periods from three different locations, each characterized by a different degree of algal abundance. The levels of the algal bisindole alkaloid caulerpin, which is accumulated in the fish tissues, was used as an indicator of the trophic exposure to the seaweed and related to the plasma metabolic profiles. The profiles appeared clearly influenced by the sampling period beside the content of caulerpin, while the analyses also supported a moderate alteration of lipid and choline metabolism related to the Caulerpa-based diet.