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SummarySignificant efforts are increasingly directed towards identifying novel therapeutic targets for autism spectrum disorder (ASD) with a rising role of aberrant glutamatergic transmission in the pathogenesis of ASD-associated cellular and behavioral deficits. This study aimed at investigating the role of chronic memantine (20 mg/kg/day) and aripiprazole (3 mg/kg/day) combination therapy in the management of prenatal sodium valproate (VPA)-induced autistic-like/cognitive deficits in male Wistar rats. Pregnant female rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like behaviors in their offspring. Prenatal VPA induced autistic-like symptoms (decreased social interaction and the appearance of stereotyped behavior) with deficits in spatial learning (in Morris water maze) and cognitive flexibility (in the attentional set-shifting task) in addition to decreased hippocampal protein levels of phosphorylated cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and gene expression of glutamate transporter-1 (Glt-1) with a decline in GABA/glutamate ratio (both measured by HPLC). These were accompanied by the appearance of numerous neurofibrillary tangles (NFTs) with enhanced apoptosis in hippocampal sections. Memantine/aripiprazole combination increased the protein levels of p-CREB, BDNF, and Glt-1 gene expression with restoration of GABA/glutamate balance, attenuation of VPA-induced neurodegenerative changes and autistic-like symptoms, and improvement of cognitive performance. This study draws attention to the favorable cognitive effects of memantine/aripiprazole combination in autistic subjects which could be mediated via enhancing CREB/BDNF signaling with increased expression of astrocytic Glt-1 and restoration of GABA/glutamate balance, leading to inhibition of hippocampal NFTs formation and neuronal apoptosis.

Trimethoprim-sulfamethoxazole is an active agent against Burkholderia pseudomallei and is being used in intensive and maintenance phases of melioidosis therapy. In this study, we evaluated the bactericidal activities of β-lactams (imipenem, ceftazidime and amoxicillin- clavulanate) alone and in combinations with trimethoprim-sulfamethoxazole against B. pseudomallei . Four clinical strains of B. pseudomallei were selected based on different genotypes that are frequently found in Malaysia. The minimum inhibitory concentrations of trimethoprim-sulfamethoxazole, ceftazidime, imipenem and amoxicillin-clavulanate were determined using microdilution broth method. The bactericidal activities and synergy effects of β-lactams and/or trimethoprim-sulfamethoxazole were evaluated by checkerboard and static time-kill analyses at 1×MIC concentration of each antibiotic. Using checkerboard method, the β-lactam/trimethoprim-sulfamethoxazole combinations exhibited ΣFIC of 0.75-4.00. In time-kill analysis, ceftazidime/trimethoprim-sulfamethoxazole combination demonstrated synergy against three strains (less 2.25-2.41 log

Herein, an efficient and scalable synthesis of 2,4-diaryl substituted chromene [43-b] pyridine derivatives, using a multicomponent reaction strategy by microwave irradiation of 4-amino 2-oxo- 2H-chromene, aromatic aldehydes, and substituted anilines is described. This synthetic strategy was found to be very useful as it follows environment benign protocol. Also it gives a good outcome in terms of yield and requires a shorter reaction time.

The correlation between pulmonary function and hypertension remains ambiguous. This study therefore determined the relationship between pulmonary function and hypertension among adult subgroup in Malaysia.Data for this study were obtained from an ongoing Prospective Urban Rural Epidemiology- Rural Urban Study (PURE RUS) , which is a prospective cohort study done by MARA University of Technology (UiTM) Medical Faculty research team to track risk factors, changing lifestyles, and chronic diseases in rural and urban population. The inclusion criteria included: Malaysian citizen, age 18-80 years, not on any anti-hypertensive agents, and able to perform lung function test. 1640 participants satisfied the criteria and were recruited in this study.From the studied population, males comprised 43.5% of them and female comprised 56.5%. A significant inverse relationship was found between pulmonary function and systolic blood pressure in both sexes measured by forced vital capacity (FVC) and Forced Expiratory Volume in 1 second (FEV1). A substantial inverse relationship was also found between pulmonary function and age, and there was a profound positive association between blood pressure and age. No major disparities were significant in pulmonary function between hypertensive and age-matched normotensive participants.Even though a substantial inverse relationship was evident between systolic blood pressure and pulmonary function, its precise clinical importance needs to be further explored particularly when age can influence both pulmonary function and blood pressure. Clearly, the impact of age has to be removed before FVC can be used as a prognosticator of hypertension.

Cochlear implantation (CI) in children with sensorineural hearing loss (SNHL) before 12 months of age (mo) improves language outcomes. MRI is important to assess CI candidacy. Anesthesia before 3 years old may increase risk of neurocognitive delay. Natural sleep MRI (NS-MRI) is an emerging technique to avoid anesthesia in infants, but relies on successful sleep for adequate imaging. Our multidisciplinary team hypothesized the following predictors of successful NS-MRI for CI evaluation: age, distance travelled, comorbidities, primary language, insurance type, HL characteristics, time and duration of MRI.We performed retrospective review of children 0-12mo who attempted NS-MRI. The NS-MRI was successful if imaging was sufficient for definitive clinical management per the managing otolaryngologist.Among 26 patients (29 scans), the median age was 3.2mo (range: 1.2-6.8mo), distance travelled was 16.3 miles (range: 0.9 to 365 miles), 12 (46%) children had medical comorbidities. 8 (31%) had public insurance. 10 (38%) had bilateral HL. 52% (15/29) of scans were successful. Patients with comorbidities had significantly lower odds of successful NS-MRI (OR 0.09; 95% CI 0.01-0.54). Success was not associated with age, distance travelled, insurance type, primary language, HL characteristics, time or duration of MRI on univariable analysis. All 11 children who failed NS-MRI underwent hearing-aid fitting and/or imaging with sedation and CI as clinically indicated before 12mo.NS-MRI was successful in 52% of infants, regardless of age, demographics, HL or MRI characteristics. Unsuccessful NS-MRI did not result in delayed intervention. NS-MRI is an effective consideration for a broad range of infants with SNHL.

Background: A series of new zerumbone hydrazones 5a-f and 9a-f have been synthesized in via an in situ procedure in high yields. The structure of synthesized compounds has been confirmed using 1H, 13C NMR and HR-MS. The bioassay result showed that several compounds exhibited cytotoxic effects against three human cancer cell lines, including HepG-2, SK-LU-1, and MCF-7. Compound 9a showed the best cytotoxic effect against HepG-2, SK-LU-1, and MCF-7 with IC50 values of 8.20, 6.66, and 9.35 μM, respectively. Objective: This study aims at developing new zerumbone hydrazones as anticancer agents based on zerumbone, a natural compound wildly growing in Vietnam. Methods: A series of new zerumbone hydrazones was designed, synthesized, and evaluated for cytotoxicity against three human cancer cell lines, including HepG-2, MCF-7, and SKLu-1, using the MTT method. Results: The bioassay result showed that several compounds exhibited cytotoxic effects against three human cancer cell lines, including HepG-2, SK-LU-1, and MCF-7. Especially, compound 9a displayed the best cytotoxic effect against HepG-2, SK-LU-1, and MCF-7 with IC50 values of 8.20, 6.66, and 9.35 μM, respectively. Conclusion: The research results suggest that some compounds could be considered as leads for the future design of zerumbone hydrazones in which bio-isosteric replacements in theortho position of the phenyl ring could be performed to improve the cytotoxic activity.

Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Malaysia. The gold standard treatment of NPC is radiotherapy (RT), as NPC is a radiosensitive tumour. Although RT is successful in treating NPC, patients cannot avoid the resulting RT complications. Oral mucositis is the most frequently encountered debilitating complication of RT and has no specific preventive treatment. The aim of this study was to evaluate the efficacy and safety of a 2.5% propolis mouthwash for preventing RT-induced mucositis in patients with NPC.The study was a prospective, double-arm, randomised control trial with intervention. The patients were randomly divided into an experimental group receiving propolis mouthwash and a placebo group receiving normal saline mouthwash. All patients were instructed to rinse their mouths with 7mL mouthwash three times daily for six weeks. The severity of oral mucositis was then evaluated by the World Health Organization Oral Toxicity Scale at the second, fourth, and sixth weeks of the study.In total, 17 patients completed the study: 10 patients used the propolis mouthwash and seven used the placebo mouthwash. The mean mucositis scores for the propolis mouthwash compared to the placebo at the second, fourth, and sixth weeks were 0.10 vs. 1.14, 0.50 vs. 2.00, and 1.20 vs. 2.86, respectively, and the differences between the two groups were statistically significant (p0.001).A 2.5% propolis mouthwash was both safe and effective for reducing the severity of oral mucositis following RT for NPC.

Oxidative stress induced neurotoxicity is increasingly perceived as an important neuropathologic mechanism underlying the motor and behavioral phenotypes associated with Huntington's disease (HD). Repeated exposure to 3-nitropropionic acid (3-NP) induces neurotoxic changes which closely simulate the neuropathological and behavioral characteristics of HD. This study aimed at evaluating the prophylactic effects of the dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) inhibitor "harmine" against 3-NP-indued neurotoxicity and HD-like symptoms. The potential prophylactic effect of harmine (10 mg/kg/day; intraperitoneal) was investigated on 3-NP-induced motor and cognitive HD-like deficits, nuclear factor erythroid 2 like 2 (NRF2), AMP kinase (AMPK) and p21 protein levels and the gene expression of haem oxygenase-1 (Ho-1), NAD(P)H: quinone oxidoreductase-1 (Nqo-1) and p62 in addition to redox imbalance and histological neurotoxic changes in the striatum, prefrontal cortex, and hippocampus of male Wistar rats. Harmine successfully increased the protein levels of NRF2, AMPK and p21 and the gene expression of Ho-1, Nqo-1 and p62, restored redox homeostasis, and reduced CASPASE-3 level. This was reflected in attenuation of 3-NP-induced neurodegenerative changes and improvement of rats' motor and cognitive performance. This study draws attention to the protective role of harmine against 3-NP-induced motor and cognitive dysfunction that could be mediated via enhancing NRF2-mediated signaling with subsequent amelioration of oxidative stress injury via NRF2 activators, p21 and AMPK, in the striatum, prefrontal cortex, and hippocampus which could offer a promising therapeutic tool to slow the progression of HD.

Background: sedentary lifestyle has been found to influence cognitive impairment, whereas physical activity and diet have been found to reduce the negative impacts of a sedentary lifestyle. Objectives: This study aims to examine the synergistic effects of the black mulberry, sunflower seed, and pumpkin seed supplements, including exercise on cognitive performance among sedentary university students. Subjects and Methods: Participants (n=36) were randomly assigned to receive black mulberry, sunflower seed, and pumpkin seed with and without exercise for 60 days. Then, they were required to complete cognitive task assessment for domain attention (visual reaction time and auditory reaction time), perception (fast counting and basic music) and executive (Eriksen flanker task and Stroop test) on day 0 (baseline), 30, and 60 of the experiment. Following that, blood samples were collected and analyzed for malondialdehyde serum concentration as an oxidative stress marker. Results: All participants showed significant faster reaction time in cognitive tasks for domain attention and basic music test for domain perception on day 30 and 60 compared to day 0. However, no significant changes were observed within group, on cognitive task for domain executive. In comparison between the groups, participants in group treatment showed significant faster reaction time for cognitive tasks for domain attention and for Erikson flanker task for domain executive as compared to group exercise alone, and group treatment with exercise. For domain perception (basic music test), participants in group treatment with exercise achieved faster reaction time compared to group treatment and exercise alone. Despite the reduction of malondialdehyde concentration in all groups, no significant difference was found between them. Conclusion: It was indicated from the findings that the consumption of black mulberry fruit extract, sunflower seeds, and pumpkin seeds with and without exercise independently enhanced attention, perception, and executive function among sedentary young adults.

The purpose of this research is to find out; The value of Islamic education and traditional values contained in the Mandi Safardi procession, Jin City Village, Atinggola District, North Gorontalo Regency.The method used is a qualitative method, the data is obtained through observation, interviews, and documentation. The data were then analyzed using reduction, display, and verification techniques, while the validity of the data was obtained by using triangulation techniques with methods and sources.The results of this study indicate that the Safar Bathing Tradition is believed to have existed since their ancestors first occupied the Jin City Village area. The Safar Bathing tradition carried out by the Jin City Village community contains Islamic educational values, namely: Worship Values, Moral Values, Moral Values, and Aqidah Values, 4) The Safar Bathing Tradition is maintained and passed down from generation to generation by the Jin City Village community. can be seen as an expressive symbol of the Jin City Village community Inspired by constitutive (religious) symbols that have a corelative-integrative and dynamic relationshipSuggestions from this research include; The Mandi Safar tradition as an ancestral cultural heritage should continue to be preserved for future generations by not eliminating the local Indonesian religious and cultural values contained in it as a medium for introducing ancestral traditions that are full of moral and religious values without ignoring the shari'ah. Islam in practice.

Lichenoid uvula mass is an unusual entity and the clinicopathologic entities are important for the diagnosis. In this case report, we report an elderly lady presented with dysphagia and "hot potato voice" due to a lichenoid uvula mass. Apart from muffled voice, the other associated symptoms are dysphagia, sore throat, globus pharyngeus and snoring. She was a non-smoker, and not on any medications except for hypertension and dyslipidaemia. Apart from the enlarged uvula, other parts of the oral cavity, oropharynx and larynx were normal. She has no other signs such as cutaneous lesions. The mass was excised under general anaesthesia followed by resolution of symptoms. Awareness of this entity, the clinical and histopathological features should be highlighted to differentiate it from other diagnosis.

Nowadays, grid-connected active dc distribution systems are gaining widespread acceptance due to the remarkable development of the dc technology, high penetration levels of dc loads, and the market availability of dc-based distributed generators. One of the main features of dc systems is the elimination of multiple conversion stages required for variable frequency ac loads, such as variable-speed drive applications; therefore, dc distribution systems are considered as an efficient and cost-effective choice for supplying such dynamic loads. Induction motors (IMs) equipped with open-loop constant voltage/frequency $(V/f)$ variable speed drives are considered as the workforce for many industrial loads due to their simplicity and satisfactory dynamic performance. However, $V/f$ IM drives exhibit poor stability dynamics, particularly, at low-speed operation, which might negatively interact with the dc distribution system, leading to further stability degradation. Therefore, this paper investigates the interaction dynamics and the performance of a grid-connected dc distribution system with a high penetration level of dynamic loads. A detailed small-signal model of the entire system is developed to characterize the overall system stability margins with the help of the eigenvalues and impedance-based analysis. Moreover, the uncertainties affecting the marginal stability such as motor operating speed, dc feeder length, and bus capacitance, are thoroughly addressed. It has been found that the dynamic loads in grid-connected dc distribution systems would exhibit instability issues due to various dynamic interactions; therefore, two different stabilizing compensation methods are proposed to mitigate the associating instability issues and enhance the system damping capability. Detailed time-domain non-linear simulations and experimental results are presented to validate the analytical results.

Background A-to-I RNA editing represents a new player in the pathogenesis of cancer. However, the knowledge of RNA editing process in cancer is still limited and represents only the tip of the iceberg. The ADAR gene family regulate the dynamic landscape of RNA editing. Aberrant RNA editing status played a vital role in the pathogenesis of hepatocellular carcinoma (HCC). The nutri-epigenomic agent- pterostilbene- exhibits anti-inflammatory, antioxidative and antiproliferative activities. However, the effect of pterostilbene on ADAR(s) expression in HCC was not studied before. Aim of the work to evaluate the potential effect of pterostilbene administration on Adar(s) expression in HCC rats. Materials and methods Twenty four adult male rats were randomly divided into 4 groups: the control group, untreated HCC group received diethylnitrosamine (DENA) for 14 weeks, HCC group take received pterostilbene and DENA for 14 weeks, and non-HCC rats were given pterostilbene for 14 weeks. These groups were subjected to histological examination of liver tissues, laboratory measures (serum albumin, ALT, AST, and α fetoprotein), and Adar(s) expression by real time-PCR. Results liver enzymes (ALT, AST) and α fetoprotein levels in treated HCC group were significantly lower than untreated HCC group (p Conclusions pterostilbene had a beneficial effect on HCC and it may alleviate the aberrant expression of Adar1 in HCC rats. Key words HCC, ADARs, pterostilbene, RNA editing enzymes. Acknowledgments: No finical support was present Conflict of interest: the authors declared that no conflicts of interest concerning the article. Authors’ contributions: The authors contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript

Worldwide, HCC is the sixth most common malignancy and the third most common cause of cancer-related death. RNA epigenetics becomes a hot topic in recent years. Among more than a hundred different RNA modifications, m6A is the most abundant modification. m6A is involved in regulating mRNA stability, splicing, and translation. However, the implications of m6A modification in human carcinogenesis remain poorly understood. METTL3 is a major RNA methyltransferase implicated in mRNA biogenesis, decay, and translation control through m6A modification. We aimed to target METTL3 in HepG2 cell lines by siRNA (small interfering RNA), and then evaluated the effect of this interference on viability and proliferative activity of HepG2 cells. Material and methods Using HepG2 cell lines, METTL3 was targeted using siRNA. The viability of HepG2 was conducted by Trypan blue exclusion test. The cell proliferation was tested by CellTiter 96® AQueous One Solution Cell Proliferation Assay. Results viable cell number and viability percent were significantly reduced in HepG2 cells transfected with siMETTL3 compared to mock cell lines (treated with transfection reagent only) (p Conclusions Knockdown of METTL3 in HepG2 cell lines successively reduced cell viability and active proliferative cell count. METTL3 may be involved in liver tumorigenesis and its targeting may be of therapeutic benefit.

Background Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the most common cause of death in people with chronic liver diseases. In Egypt, liver cancer forms 11.75% of the malignancies of all digestive organs and 1.68% of the total malignancies. HCC constitutes 70.48% of all liver tumors among Egyptians. In the past few years, early diagnosis and advances in therapeutic measures have greatly improved the outcome of HCC patients. However, the prognosis is still poor with overall survival rates of 3-5%. The alterations in cancer driver genes and associated pathways are the major triggers for HCC. So, the identification and targeting of these genes are beneficial to understand HCC and to develop a new therapy. Aim of the work We aimed to target CTNNB1 and RAB1A oncogenes in HepG2 cell lines by RNAi then evaluate the effect of their targeting on the viability and proliferative activity of HepG2 cells. Materials and methods Using HepG2 cell lines, CTNNB1 & RAB1A oncogenes were targeted using two different siRNAs (small interfering RNA) for each gene. The viability of HepG2 was conducted by Trypan blue test. The cell proliferation was tested by CellTiter 96® AQueous One Solution Cell Proliferation Assay. Results There was significant reduction in the cells’ viability detected by trypan blue test in transfected cells with siRNA targeting either CTNNB1 or RAB1A compared to Mock HepG2 cell lines (p Conclusion Targeting CTNNB1or RAB1A in HepG2 cell lines decreased the cell viability and proliferative activity. Moreover, targeting CTNNB1 was effective in decreasing cell proliferative activity compared to targeting RAB1A in HepG2 cell lines. So, targeting CTNNB1 may have a potential therapeutic effect in treatment of HCC.

No abstract provided.

The knowledge of RNA editing modifications and its subsequent proteomic diversity in is still limited and represents only the tip of the iceberg. Adenosine to inosine (A-to-I) RNA editing is the most prevalent in RNA editome with a rising role for ADARgene family as a major regulator of the dynamic landscape of RNA editing. This study aimed at evaluating the potential chemopreventive effects of the epigenetic regulator "pterostilbene" in diethylnitrosamine (DEN)-exposedrat model. Consequently, the hepatic Adars expression was investigated as a possible mechanism for mediation of the putative pterostilbene-induced chemopreventive effect. The effects of administration of pterostilbene were investigated on the structural changes, immunohistochemical staining, liver function test, serum alpha feto-protein (AFP), IL-6, and hepatic Adar1 and Adar2 relative gene expression at the beginning and at the 6th week of the study. Pterostilbene attenuated DEN-induced liver injury, improves hepatocyte parrafin-1 (Hep Par-1), decreases heat shock protein 70 (HSP70), improved AFP, serum albumin, transaminases, IL-6 with alleviation of disturbed hepatic Adar1 and Adar2 expression. This study spotlights the role of pterostilbene in attenuation of DEN-induced liver injury which could be mediated, at least partially, through the alleviation of the aberrant expression of Adar enzymes. Yet, more in-depth studies are needed to further elucidate the molecular mechanisms underlying the effects of pterostilbene on RNA editing enzymes.

Background: Fecundity is an important parameter in fisheries that predicts the reproductive capability of fish stock. Information on the fecundity of Common carp is helpful in estimating the amount of offspring produced in spawning season, which is essential for the stock assessment of the species. Assessment of the fecundity of a fish is essential for evaluating the commercial potentialities of its stock, life history, practical culture and actual management of the fishery. Common carp is a commercially important fish which has the potential to meet the demand of food in the country. Scanty of data is available on fecundity parameter of common carp in Kashmir waters. Therefore, this research work aims to estimate the fecundity of Common carp collected from the Dal lake of Kashmir. Methods: The present study aims to estimate the fecundity of Common carp, [Cyprinus carpio var. communis] existing in Dal Lake, Kashmir. The 30 fish samples were collected once every month from the month of January 2018 to December 2018. Fishes were brought to Fisheries Resource Management (FRM), Faculty of Fisheries, SKUAST-K Laboratory for the estimation of total length, weight of fishes and weight of ovaries. Gravimetric and actual counting method was used for the estimation of fecundity. Result: It was observed that the number of eggs varied from 16650 (for a fish with total length 180mm and total weight 120 g) to 129000 (for a fish with total length 430 mm and total weight 1300 g. The mean absolute fecundity was recorded as 68864.07± 6563.59 for a fish with a mean total length of 301.43 ± 13.93 mm and mean total weight of 435.1 ± 66.51 g. The relative fecundity ranged from 99.2-240.8 and the mean relative fecundity was 185.96. Significant positive correlation was found between fish weight and absolute fecundity. (r= 0.907, p less than 0.01), fish length and absolute fecundity (r= 0.976, p less than 0.01), Ovary weight and absolute fecundity (r= 0.998, p less than 0.01). Relative fecundity showed a significant negative correlation with weight, length and absolute fecundity (r= -0.747, p less than 0.01; r= -0.419, p less than 0.05 and r= -0.460, p less than 0.05 respectively.

ImportanceA genetic diagnosis can help elucidate the prognosis of hearing loss, thus significantly affecting management. Previous studies on diagnostic yield of hearing loss genetic tests have been based on largely homogenous study populations.ObjectivesTo examine the diagnostic yield of genetic testing in a diverse population of children, accounting for sociodemographic and patient characteristics, and assess whether these diagnoses are associated with subsequent changes in clinical management.Design, Setting, and ParticipantsThis retrospective cohort study included 2075 patients seen at the Children’s Communications Clinic, of whom 517 completed hearing loss gene panel testing between January 1, 2015, and November 1, 2021, at the University of California, San Francisco Benioff Children’s Hospital system. From those 517 patients, 426 children with at least 2 audiograms were identified and analyzed. Data were gathered from November 2021 to January 2022 and analyzed from January to February 2022.Main Outcomes and MeasuresThe measures of interest were sociodemographic characteristics (age at testing, gender, race and ethnicity, primary language, and insurance type), hearing loss characteristics, and medical variables. The outcome was genetic testing results. Variables were compared with univariate and multivariable logistic regression.ResultsOf the 2075 patients seen at the Children’s Communications Clinic, 517 (median [range] age, 8 [0-31] years; 264 [51.1%] male; 351 [67.9%] from an underrepresented minority [URM] group) underwent a hearing loss panel genetic test between January 1, 2015, and November 1, 2021. Among those 517 patients, 426 children (median [range] age, 8 [0-18] years; 221 [51.9%] male; 304 [71.4%] from an URM group) with 2 or more audiograms were included in a subsequent analysis. On multivariable logistic regression, age at testing (odds ratio [OR], 0.87; 95% CI, 0.78-0.97), URM group status (OR, 0.29; 95% CI, 0.13-0.66), comorbidities (OR, 0.27; 95% CI, 0.14-0.53), late-identified hearing loss (passed newborn hearing screen; OR, 0.27; 95% CI, 0.08-0.86), and unilateral hearing loss (OR, 0.04; 95% CI, 0.005-0.33) were the only factors associated with genetic diagnosis. No association was found between genetic diagnosis yield and other sociodemographic variables or hearing loss characteristics. Patients in URM and non-URM groups had statistically similar clinical features. A total of 32 of 109 children (29.4%) who received a genetic diagnosis received diagnoses that significantly affected prognosis because of identification of syndromic or progressive sensorineural hearing loss or auditory neuropathy spectrum disorder relating to otoferlin.Conclusions and RelevanceThis cohort study’s findings suggest that genetic testing may be broadly useful in improving clinical management of children with hearing loss. More research is warranted to discover and characterize diagnostic genes for those who have been historically underrepresented in research and medicine.

The β-cyclodextrin shell of synthesized silver nanoparticles (βCD-AgNPs) are found to enhance the detection of hydrogen peroxide in urine when compared to the Horse Radish Peroxidase assay kit. Nanoparticles are confirmed by the UV-Vis absorbance of their localized surface plasmonic resonance (LSPR) at 384 nm. The mean size of the βCD-AgNPs is 53 nm/diameter, XRD analysis shows a face-centered cubic structure. The crystalline structure of type 4H hexagonal nature of the AgNPs with 2.4 nm β-CD coating onto is confirmed using aberration corrected high-resolution transmission electron microscopy (HRTEM). A silver atomic lattice at 2.50 Å and 2.41 Å corresponding to (100) and (101) Miller indices is confirmed using the HRTEM. The scope of βCD-AgNPs to detect hydrogen peroxide (H2O2) in aqueous media and human urine is investigated. The test is optimized by examining the effect of volumes of nanoparticles, the pH of the medium, and the kinetic and temperature effect on H2O2 detection. The βCD-AgNPs test is used as a refined protocol, which demonstrated improved sensitivity towards H2O2 in urine compared to the values obtained by the Horse Radish Assay kit. Direct assessment of H2O2 by the βCD-AgNPs test presented always with a linear response in the nM, μM, and mM ranges with a limit of detection of 1.47 nM and a quantitation limit of 3.76 nM. While a linear response obtained from 1.3 to 37.3 nmoles of H2O2/mole creatinine with a slope of 0.0075 and regression coefficient of 0.9955 when the βCD-AgNPs is used as refined test of creatinine. Values ranging from 34.62 ± 0.23 nmoles of H2O2/mole of creatinine and 54.61 ± 1.04 nmoles of H2O2/mole of creatinine when the matrix is not diluted and between 32.16 ± 0.42 nmoles of H2O2/mole of creatinine and 49.66 ± 0.80 nmoles of H2O2/mole of creatinine when the matrix is twice diluted are found in freshly voided urine of seven apparent healthy men aged between 20 and 40 years old.