Toxicological evaluation of therapeutically active zinc oxide nanoflowers in pre-clinical mouse model.

Our earlier reports established that zinc oxide nanoflowers (ZONF) show significant pro-angiogenic properties, where reactive oxygen species, nitric oxide and MAPK-AKT-eNOS cell signaling axis play an essential task. Considering the significance of angiogenesis in healthcare, our research group has recently demonstrated the in vivo therapeutic application of ZONF (10 mg/kg b.w.) for treating peripheral artery disease. Moreover, based on the angio-neural crosstalk between vascular and neuronal systems, we have further demonstrated the neuritogenic and neuroprotective characteristics of pro-angiogenic nanoflowers (10 mg/kg b.w.) for the treatment of cerebral ischemia. However, it is crucial for a therapeutic material to be non-toxic for its practical clinical applications and therefore assessment of its in vivo toxicity and adverse effect is highly important. Herein, for the first time, we investigate a detailed nanotoxicology of therapeutically active ZONF in Swiss albino mice to evaluate their safety profile and comprehend their aspects for future clinical applications. The maximum tolerated dose (MTD) of ZONF was found to be 512.5 mg/kg b.w. which was employed for acute exposure (2 weeks), showing slight toxicity. However, sub-chronic (4 weeks) and long term chronic (8-12 weeks) studies of nanoflowers exhibited their non-toxic nature particularly at lower therapeutic doses (1-10 mg/kg b.w.). Additionally, in depth genotoxicity study revealed that lower therapeutic dose of ZONF (10 mg/kg b.w.) did not exhibit significant toxicity even in genetic level. Overall, the present nanotoxicology of ZONF suggests their high biocompatible nature at therapeutic dose, offering the basis of their future clinical applications in ischemic and other vascular diseases.

Clastogenic, aneugenic, and tubulin polymerization properties of di-(2-ethylhexyl) phthalate and dibutyl phthalate.

Phthalate compounds were found to disrupt the endocrine system and alter transcriptomes during human embryonic development. In our previous work, we have isolated and reported two such phthalates di-(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) from Brevibacterium mcbrellneri bacteria and evaluated their bioactive properties. Naturally derived phthalates might be less toxic compared with synthesized molecules. We have investigated biologically isolated phthalates to understand the possible genotoxic effects in mice and further investigated in silico binding and polymerization of ß-tubulin. Three sub-lethal concentrations of DEHP (150 µM, 175 µM, and 200 µM) and DBP (10 µM, 15 µM, and 30 µM) were studied. The results showed that the phthalates were found to be highly genotoxic in nature. However, the pattern of genotoxic effects was not found to be dose-dependent in the induction of chromosome aberrations (CA), micronuclei (MN), and changes in the mitotic index (MI) in cells. In silico studies of phthalates on polymerization of ß-tubulin suggested that both DBP and DEHP were able to interact with the hydrogen bonds and make strong van der Waals interactions with ß-tubulin thereby possibly causing destabilization of microtubule network. Our study suggests that these phthalates might be playing an important role in normal cell division thereby showing highly genotoxic effects.

In vitro and in vivo antimalarial activity of green synthesized silver nanoparticles using Sargassum tenerrimum - a marine seaweed.

Green nanotechnology has recently attracted a lot of attention as a potential technique for drug development. In the present study, silver nanoparticles were synthesised by using Sargassum tenerrimum, a marine seaweed crude extract (Ag-ST), and evaluated for antimalarial activity in both in vitro and in vivo models. The results showed that Ag-ST nanoparticles exhibited good antiplasmodial activity with IC50 values 7.71±0.39 µg/ml and 23.93±2.27 µg/ml against P. falciparum and P. berghei respectively. These nanoparticles also showed less haemolysis activity suggesting their possible use in therapeutics. Further, P. berghei infected C57BL/6 mice were used for the four-day suppressive, curative and prophylactic assays where it was noticed that the Ag-ST nanoparticles significantly reduced the parasitaemia and there were no toxic effects observed in the biochemical and haematological parameters. Further to understand its possible toxic effects, both in vitro and in vivo genotoxicological studies were performed which revealed that these nanoparticles are non-genotoxic in nature. The possible antimalarial activity of Ag-ST may be due to the presence of bioactive phytochemicals and silver ions. Moreover, the phytochemicals prevent the nonspecific release of ions responsible for low genotoxicity. Together, the bio-efficacy and toxicology outcomes demonstrated that the green synthesized silver nanoparticles (Ag-ST) could be a cutting-edge alternative for therapeutic applications.

A Questionnaire-based Study on Perceptions, Attitudes, and need Assessment regarding Geriatric Healthcare among Geriatric Outpatients at a Tertiary Care Hospital in India.

BACKGROUND: The lack of specialized geriatric healthcare in India, coupled with an aging population, has resulted in longer wait times, communication barriers, and a potential increase in unmet needs in a demographic that is already financially and socially vulnerable. This raises the need for exploring the perspectives and needs of the geriatric patient population to improve the quality and accessibility of the healthcare they receive. OBJECTIVES: This study was conducted to assess the perceptions and perceived needs of geriatric patients regarding current healthcare and their attitudes toward specialized geriatric healthcare. MATERIALS AND METHODS: Following the Institutional Ethics Committee (IEC), a cross-sectional study was carried out among 262 geriatric patients (age >60) from seven outpatient departments (OPD). A structured 10-item questionnaire was administered to assess the perceptions and perceived needs of the study population. RESULTS: A total of 165 (63%) patients were not satisfied with the healthcare being provided to them. Around 96.1% of patients felt the need for a separate geriatric OPD/department. A total of 98% of patients had optimistic attitudes toward the possibility of specialized geriatric healthcare. A total of >80% of the patients were willing to spend more time for checkups and follow-ups regularly if that would improve their quality of life. CONCLUSION: This study showed a low satisfaction rate of geriatric patients with the current healthcare and a high felt need for specialized geriatric facilities. There was an overall positive attitude of patients toward the implementation of various facilities of specialized geriatric healthcare.

Nuclear envelope protein lamin B receptor protects the genome from chromosomal instability and tumorigenesis.

Lamin B Receptor (LBR) is an inner nuclear membrane protein that assembles the nuclear envelope post mitosis. Here we show that LBR depletion induces mitotic defects accompanied by recurrent chromosomal losses. In addition, LBR knockdown results in nuclear aberrations such as nuclear blebs and micronuclei, with chromosomes showing higher frequency of losses, being enriched within the micronucleus. Furthermore, doxycycline-induced conditional depletion of LBR significantly increased tumor volumes that form within the subcutaneous xenografts of mice. Of note, the tumor-derived primary cells recapitulated chromosomal losses and gains, revealing a novel role for LBR as a tumor suppressor. Co-immunoprecipitation of LBR uncovered an association of LBR with telomere-associated factors. Interestingly, qPCR array-based gene expression profiling showed a significant upregulation of telomere repeat-binding factor 1 (TRF1) upon LBR depletion. Remarkably, TRF1 knockdown in the background of LBR depletion maintains chromosomal stability, unraveling a novel mechanism involving LBR and TRF in the maintenance of chromosomal stability in colorectal cancer cells.

Race/Ethnicity, Gender, and Socioeconomic Status Representation in U.S.-Based Randomized Controlled Trials of Tinnitus: A Systematic Review.

PURPOSE: The purpose of this study was to investigate if peer-reviewed randomized controlled trials (RCTs) for the management/treatment of tinnitus conducted in the United States include diverse participants in terms of gender, race/ethnicity, education, occupation, and income. METHOD: We performed a comprehensive and systematic literature search via PubMed, Web of Science, Clinical-Trials.gov, and the Cochrane Central Register of Controlled Trials. Our goal was to identify prospective RCTs of tinnitus intervention conducted in the United States from January 1994 to September 2021 and published in peer-reviewed journals. RESULTS: A total of 2,584 studies were retrieved. Thirty-two peer-reviewed articles met all inclusion criteria. Of the included studies, approximately 96% reported participants' gender. Approximately 15% studies reported race/ethnicity information in alignment with the U.S. Census Bureau. However, an underrepresentation of both females and people of color was evident across studies. Reporting of socioeconomic status information of participants was also scarce, with only 25% studies reporting education and/or occupation of participants and 0% reporting income levels. CONCLUSIONS: This study indicates underrepresentation and underreporting of diverse participant pools in tinnitus research. Reasons for such underrepresentation are explored. Additionally, this systematic review indicates that recent research in tinnitus portrays an optimistic trend in terms of reporting and recruitment of diverse participant groups. Sustainable strategies for including diverse research participants are essential for hearing health care equity. Research and strategies to promote this goal are discussed.

In Vitro and In Vivo Anticancer and Genotoxicity Profiles of Green Synthesized and Chemically Synthesized Silver Nanoparticles.

Silver nanoparticles were green synthesized (Ag-PTs) employing the crude extract of Padina tetrastromatica, a marine alga, and their anticancer and safety profile were compared with those of chemically synthesized silver nanoparticles (Ag-NPs) by in vitro and in vivo models. Ag-PT exhibited potent cytotoxicity against B16-F10 (IC50 = 3.29), MCF-7 (IC50 = 4.36), HEPG2 (IC50 =3.89), and HeLa (IC50 = 4.97) cancer cell lines, whereas they exhibited lower toxicity on normal CHO-K1 cells (IC50 = 5.16). The potent anticancer activity of Ag-PTs on cancer cells is due to the liberation of ions from the nanoparticles. Increased ion internalization to the cells promotes reactive oxygen species (ROS) production and ultimately leads to cell death. The in vitro anticancer results and in vivo melanoma tumor regression study showed significant inhibition of melanoma tumor growth due to Ag-PT treatment. Ag-PT is involved in the upregulation of the p53 protein and downregulation of Sox-2 along with the Ki-67 protein. The antitumor effects of Ag-PTs may be due to the additional release of ions at a lower pH of the tumor microenvironment than that of the normal tissue. The results of safety investigations of Ag-PT by studying mitotic chromosome aberrations (CAs), micronucleus (MN) induction, and mitotic index (MI) demonstrated Ag-PT to be less genotoxic compared to Ag-NP. The bioefficacy and toxicology outcomes together demonstrated that the green synthesized silver nanoparticles (Ag-PTs) could be explored to develop a biocompatible, therapeutic agent and a vehicle of drug delivery for various biomedical applications.

Comprehensive Geriatric Assessment (CGA) Screening of Geriatric Patients in a Tertiary Care Hospital: a Cross-sectional Study in India.

BACKGROUND: Within the next few decades, India will witness a staggering increase in its elderly population owing to advancements in health care. However, an increase in life span is not mutually inclusive with high quality of living. Old age is associated with multiple ailments which decreases functionality and increases dependency, several of which go undiagnosed while catering to primary complaints. This prompts the need for a comprehensive approach to the healthcare of the elderly for which Comprehensive Geriatric Assessment (CGA is widely practiced in the west. OBJECTIVES: This study was conducted to estimate the prevalence of undiagnosed medical problems by Comprehensive Geriatric Assessment (CGA) Screening and explore its applicability in Indian tertiary healthcare setup. METHODOLOGY: Following ethical approval of the institute, a cross-sectional study was conducted among 262 geriatric patients with age over 60 years, from seven out-patients departments. A Comprehensive Geriatric Assessment (CGA) inventory was prepared by compiling screening instruments for Visual acuity, Hearing acuity, Dependency, Functionality, Depression, Cognitive impairment, Fall risk, Urinary incontinence, Nutritional Status and Insomnia. The participants were administered the screening inventory once they had already undergone a normal check-up in the OPDs. RESULTS: Overall, 262 geriatric patients underwent CGA screening (Female: 57.3%, Male: 42.7%). There was a high prevalence of problems going undiagnosed ranging from 58.65% to 95.45% in various OPDs. Some problems had a significantly greater overall prevalence and were also prevalent in going undiagnosed in particular OPDs (urinary incontinence in Gynaecological OPD, p=0.003; insomnia in surgical OPD, p<0.005). Many patients who screened positive for certain problems were found to have a few other problems as well (dependency and cognitive impairment, p=0.003; insomnia and depression, p=0.0001). CONCLUSION: This study showed a high prevalence of problems going undiagnosed along with their associations with particular OPDs and other problems. Participants of this study showed a considerable acceptability for CGA. This reaffirmed the need for CGA in every geriatric patient in our tertiary care setup.

Nuclear envelope, chromatin organizers, histones, and DNA: The many achilles heels exploited across cancers.

In eukaryotic cells, the genome is organized in the form of chromatin composed of DNA and histones that organize and regulate gene expression. The dysregulation of chromatin remodeling, including the aberrant incorporation of histone variants and their consequent post-translational modifications, is prevalent across cancers. Additionally, nuclear envelope proteins are often deregulated in cancers, which impacts the 3D organization of the genome. Altered nuclear morphology, genome organization, and gene expression are defining features of cancers. With advances in single-cell sequencing, imaging technologies, and high-end data mining approaches, we are now at the forefront of designing appropriate small molecules to selectively inhibit the growth and proliferation of cancer cells in a genome- and epigenome-specific manner. Here, we review recent advances and the emerging significance of aberrations in nuclear envelope proteins, histone variants, and oncohistones in deregulating chromatin organization and gene expression in oncogenesis.

Online, Asynchronous Hearing Education and Research Project for Ethnically Diverse Adolescents via Interprofessional Collaboration and Electronic Service-Learning During the COVID-19 Pandemic: A Pilot Study on the Needs and Challenges.

Purpose This study discusses the creation of an online, asynchronous presentation to educate adolescents about prevention of noise-induced hearing loss (NIHL) through interprofessional collaborations and electronic service-learning (eSL) during the COVID-19 pandemic. Method The Hearing Education and Research (HEAR) presentation, which included activities and videos to educate a group of ethnically diverse adolescents (n = 100) on NIHL, was created by 11 doctor of audiology (AuD) students through online collaborations toward course-related eSL requirements. Adolescents responded to a baseline survey to assess hearing health-related behaviors prior to reviewing the presentation. A postprogram survey was administered 1 week after the presentation to assess change in knowledge and attitudes toward NIHL prevention. Online collaborations with schoolteachers helped with project implementation. Postreflection papers written by AuD students regarding the eSL activities were analyzed. Lastly, suggestions from a focus group of educators were included that highlight the role of interprofessional collaborations to enhance school-based hearing conservation opportunities. Results The HEAR presentation resulted in changes in knowledge about NIHL among the adolescents. Postreflection papers by the AuD students indicated that the eSL activity served as a high-impact pedagogical assignment, especially during the academic challenges of the pandemic. Feedback from a focus group of schoolteachers helped outline ideas for future implementation of sustainable hearing conservation programs in school settings. Conclusion The pilot data collected in this study serve as a proof of concept for future hearing conservation projects in school-based settings via interprofessional collaborations and by engaging university students via eSL.

Awareness of the Profession of Audiology Among Ethnically Diverse Adolescents: A Pre- and Post-Education Study.

Purpose The purpose of this study was to investigate knowledge about the profession of Audiology among adolescents from diverse backgrounds before, immediately after, and 6 months after an educational program on the profession of Audiology. Method Adolescents (N = 152) from ethnically diverse backgrounds responded to a survey investigating their awareness about Audiology. Thereafter, they participated in an educational program on the profession of Audiology. One third of the participants were invited to respond to the survey immediately after the educational program. Six months after the educational program, 120 of the original sample of 152 participants responded again to the survey in order to assess if the gains from the educational program were retained. Results The results from the baseline survey indicated that approximately 25% of participants were aware about the profession of Audiology. None of the participants reported that balance assessment or management was within the scope of practice of audiologists in the baseline survey. The chi-square test indicated that the educational program resulted in significant enhancement in awareness about the profession of Audiology immediately after education. Results also indicated that the gains in knowledge were retained 6 months after education. Conclusion In light of the existing literature, it is clear that there is a need to recruit an ethnically diverse talent pool of individuals who will choose a career in Audiology in the forthcoming decades. Preliminary results from this study could be helpful in strategizing efforts to improve the visibility of Audiology to younger college aspirants. Advantages of reaching to school-age students at grassroots levels and educating them about the profession of Audiology are discussed in this article.

Efficient anti-tumor nano-lipoplexes with unsaturated or saturated lipid induce differential genotoxic effects in mice.

Cationic lipids are well-known excipients for nanometric liposomal gene delivery systems. However, because of the suspected, collateral toxicity in normal cells, the use of cationic lipids for the treatment of human tumor is largely limited. Recently, we developed a glucocorticoid receptor (GR)-targeted liposomal, anticancer delivery system (DXE nano-lipoplex), which carried cationic lipid of saturated twin aliphatic chains. It exhibited efficient anti-tumor effect in aggressive and drug-resistant tumor models. Toward exploring lipoplex's human clinical use, we incorporated another nano-lipoplex (D1XE) group that carried cationic lipid with one of its aliphatic chain carrying unsaturation and compared in vivo genotoxicological profiling-based safety assessment and the respective anti-tumor efficacy of the lipoplexes. Thus, both the lipoplexes differ only by the chemical identity of one of their constituent cationic lipid. Unsaturated aliphatic chains in lipid generally impart efficient cell surface fusogenic property in lipid formulations. Herein, we report that nanoplex with unsaturated cationic lipid (D1XE) exhibited better physical appearance with less flocculent behavior than nanoplex with saturated lipid (DXE). Upon multiple injections, D1XE nanoplex imparted better tumor regression but most importantly, exhibited much lower overall toxicity (e.g. genotoxicity, weight loss, etc.) than DXE nanoplex. With a higher antitumor effect but a lower genotoxic effect, D1XE is proved to be a better nanoplex than DXE for the potential clinical trial. Thus, this study clearly delineates the importance of incorporating a constituent lipid that carries a single unsaturated aliphatic chain toward developing efficient anti-tumor nano-lipoplexes with reduced genotoxicity.

A Study of Social Media Utilization by Individuals With Tinnitus.

PURPOSE: As more people experience tinnitus, social awareness of tinnitus has consequently increased, due in part to the Internet. Social media platforms are being used increasingly by patients to seek health-related information for various conditions including tinnitus. These online platforms may be used to seek guidance from and share experiences with individuals suffering from a similar disorder. Some social media platforms can also be used to communicate with health care providers. The aim of this study was to investigate the prevalence of tinnitus-related information on social media platforms. METHOD: The present investigation analyzed the portrayal of tinnitus-related information across 3 social media platforms: Facebook (pages and groups), Twitter, and YouTube. We performed a comprehensive analysis of the platforms using the key words "tinnitus" and "ringing in the ears." The results on each platform were manually examined by 2 reviewers based on social media activity metrics, such as "likes," "followers," and "comments." RESULTS: The different social media platforms yielded diverse results, allowing individuals to learn about tinnitus, seek support, advocate for tinnitus awareness, and connect with medical professionals. The greatest activity was seen on Facebook pages, followed by YouTube videos. Various degrees of misinformation were found across all social media platforms. CONCLUSIONS: The present investigation reveals copious amounts of tinnitus-related information on different social media platforms, which the community with tinnitus may use to learn about and cope with the condition. Audiologists must be aware that tinnitus sufferers often turn to social media for additional help and should understand the current climate of how tinnitus is portrayed. Clinicians should be equipped to steer individuals with tinnitus toward valid information.

Potential of the Bioinspired CaCO3 Microspheres Loaded with Tetracycline in Inducing Differential Cytotoxic Effects toward Noncancerous and Cancer Cells: A Cytogenetic Toxicity Assessment Using CHO Cells in Vitro.

Calcium carbonate (CaCO3)-based materials as feasible pH-sensitive drug carriers, which can actively dissolve in an acidic microenvironment of cancer cells, are finding increasing importance. This has drawn our interest in the development of a bioinspired polypeptide- mediated method to design calcium carbonate microspheres loaded with tetracycline (CaCO3-TC) with an aim to explore its safe application in cancer therapeutics. Its therapeutic application in cancer patients essentially demands its safety information on the normal cells. Herein our study presents the in vitro genetic toxicological information on CaCO3-TC using noncancerous mammalian CHO cells in comparison to bare TC at three different concentrations (100, 200, and 300 µM) selected based on the cytotoxicity data (MTT). Assessment of various end points like chromosome aberrations, micronucleus, mitotic index and effects on cell cycle distribution after 24 h post-treatment demonstrates a significant reduction in clastogenic ( P < 0.001), aneugenic potential ( P < 0.05), and nonmitotoxic nature of CaCO3-TC than that of bare TC. Noticeably, as inferred from the FACS analysis on cancer cells, G2/M phase accumulation in breast cancer cells (MDA-MB-231), and at G1 phase in cervical cancer cells (HeLa) reveal its potential anticancer property. On the other hand, the genotoxicity studies illustrate protective effects of CaCO3-TC on noncancerous cells. While the pH-dependent dissolution property of the CaCO3 matrix encasing tetracycline results in higher toxicity on cancer cells, the near neutral pH in the case of normal cells prevents complete dissolution of CaCO3 thereby not allowing the encapsulated TC to adequately interact with the cells. Therefore, thus assembled CaCO3 spheres not only provide a way for facile encapsulation of tetracycline under mild conditions but also result in an effective matrix for differential toxicity toward normal and cancer cells justifying its clinical development as a novel target-specific drug in therapeutic applications for metastatic cancers.

Effects of Long-Term Musical Training on Cortical Auditory Evoked Potentials.

OBJECTIVE: Evidence suggests that musicians, as a group, have superior frequency resolution abilities when compared with nonmusicians. It is possible to assess auditory discrimination using either behavioral or electrophysiologic methods. The purpose of this study was to determine if the acoustic change complex (ACC) is sensitive enough to reflect the differences in spectral processing exhibited by musicians and nonmusicians. DESIGN: Twenty individuals (10 musicians and 10 nonmusicians) participated in this study. Pitch and spectral ripple discrimination were assessed using both behavioral and electrophysiologic methods. Behavioral measures were obtained using a standard three interval, forced choice procedure. The ACC was recorded and used as an objective (i.e., nonbehavioral) measure of discrimination between two auditory signals. The same stimuli were used for both psychophysical and electrophysiologic testing. RESULTS: As a group, musicians were able to detect smaller changes in pitch than nonmusician. They also were able to detect a shift in the position of the peaks and valleys in a ripple noise stimulus at higher ripple densities than non-musicians. ACC responses recorded from musicians were larger than those recorded from non-musicians when the amplitude of the ACC response was normalized to the amplitude of the onset response in each stimulus pair. Visual detection thresholds derived from the evoked potential data were better for musicians than non-musicians regardless of whether the task was discrimination of musical pitch or detection of a change in the frequency spectrum of the ripple noise stimuli. Behavioral measures of discrimination were generally more sensitive than the electrophysiologic measures; however, the two metrics were correlated. CONCLUSIONS: Perhaps as a result of extensive training, musicians are better able to discriminate spectrally complex acoustic signals than nonmusicians. Those differences are evident not only in perceptual/behavioral tests but also in electrophysiologic measures of neural response at the level of the auditory cortex. While these results are based on observations made from normal-hearing listeners, they suggest that the ACC may provide a non-behavioral method of assessing auditory discrimination and as a result might prove useful in future studies that explore the efficacy of participation in a musically based, auditory training program perhaps geared toward pediatric or hearing-impaired listeners.

The Relationship Between EABR and Auditory Performance and Speech Intelligibility Outcomes in Pediatric Cochlear Implant Recipients.

PURPOSE: The primary purpose of the present study was to investigate the relationship between postimplant electrically evoked auditory brainstem response (EABR) measures (wave V threshold, wave V latency, input-output functions) and auditory performance and speech intelligibility outcomes measured using parental rating scales, such as Categories of Auditory Performance (CAP; Archbold, Lutman, & Marshall, 1995) and the Speech Intelligibility Rating scale (SIR; Allen, Nikolopoulos, Dyar, & O'Donoghue, 2001), respectively. The secondary purpose was to evaluate the relationship between age at implantation and ratings on the CAP and SIR. METHOD: Forty children with congenital sensorineural hearing loss participated. Preimplant parental ratings on the CAP and SIR were obtained, and all the children underwent cochlear implantation. Intracochlear EABRs were recorded postimplantation. Postimplant parental ratings on the CAP and SIR were obtained. The relationships between EABR parameters and auditory performance and speech intelligibility outcomes were studied. The effect of age at implantation on auditory performance and speech intelligibility outcomes was also investigated. RESULTS: A significant negative correlation was found between EABR wave V thresholds and SIR growth (r = -.415, p = .016). Children with better CAP growths tended to have lower wave V thresholds than those with poorer CAP growths. Age at implantation had an effect on the auditory performance as measured using the CAP. CONCLUSIONS: The present study provides evidence for the relationship between wave V thresholds of the intracochlear EABR and auditory performance and speech intelligibility outcomes measured using parental rating scales in pediatric cochlear implant recipients. Data also indicate that early intervention has a positive impact on auditory performance outcomes.