Auditory Neuropathy Spectrum Disorder in Individuals with Sickle Cell Anemia: Case Study.

The present study attempted to understand the association between Auditory neuropathy spectrum disorder (ANSD) and Sickle cell anemia (SCA) and to recognize possible causative factors for the presence of ANSD in SCA individuals. Two cases, 24 years male and 17years female with a laboratory-confirmed diagnosis of Sickle cell anemia underwent detailed audiological evaluation i.e., pure tone audiometry, speech audiometry, immittance audiometry, otoacoustic emission, and auditory brainstem responses. Audiological evaluation revealed a bilateral moderate low-frequency sensorineural hearing loss in male and bilateral moderately severe sensorineural Hearing loss in female case with elevated Speech Recognition Threshold and poor Speech Identification Scores. 'A' type tympanogram with the absence of Acoustic reflexes and the presence of Otoacoustic emission with no distinct and reproducible peak V in Auditory Brainstem Response (ABR) at 90 dBnHL with the presence of ringing cochlear microphonics on polarity reversal collectively indicating bilateral ANSD in both cases. ANSD and SCA are reported to have a genetic basis of etiology. There might be possibilities that one genetic condition may be common in manifesting both conditions or one genetic condition can cause the presence of another genetic condition or can exaggerate the evolution of another genetic condition. Also, abnormal ABR findings indicate the possibility of neuropathological involvement in isolation or in combination with genetic abnormalities that need detailed investigation to understand non-genetic causative factors. Thus, paved the path for further research in this line and might provide better rehabilitative options.

Preventing Cancer by Inhibiting Ornithine Decarboxylase: A Comparative Perspective on Synthetic vs. Natural Drugs.

This perspective delves into the investigation of synthetic and naturally occurring inhibitors, their patterns of inhibition, and the effectiveness of newly utilized natural compounds as inhibitors targeting the Ornithine decarboxylase enzyme. This enzyme is known to target the MYC oncogene, thereby establishing a connection between polyamine metabolism and oncogenesis in both normal and cancerous cells. ODC activation and heightened polyamine activity are associated with tumor development in numerous cancers and fluctuations in ODC protein levels exert a profound influence on cellular activity for inhibition or suppressing tumor cells. This perspective outlines efforts to develop novel drugs, evaluate natural compounds, and identify promising inhibitors to address gaps in cancer prevention, highlighting the potential of newly designed synthetic moieties and natural flavonoids as alternatives. It also discusses natural compounds with potential as enhanced inhibitors.

A quantum chemical study: thoughtful exploration for optimal donors in Y-type dual donor-based dye sensitizers.

This research explores the influence of different dual donors on the effectiveness of dye sensitizers. We selected 35 diverse donors to construct Y-type dual donor-based dyes, connecting them with thiophene as the π-spacer and cyanoacrylic acid as the acceptor. Density functional theory calculations indicate that these dual donor-based dyes exhibit superior optoelectronic properties compared to their single donor counterparts. Notably, significant variations in charge distribution among the different dual donors affect their donor capabilities. Our calculations specifically highlight the enhanced thermodynamic parameters, including light harvesting efficiency (LHE), the free energy of dye injection (ΔGinject), and regeneration (ΔGreg), for donor moieties containing nitrogen atoms, such as NS-3 (N,N-dimethylaniline), NS-5 (diphenylamine), NS-6 (triphenylamine), and NS-8 (4-methoxy-N-(4-methoxyphenyl)-N-phenylaniline). These results suggest that nitrogen-containing donor moieties act as promising candidates for donors for efficient dye sensitizers. However, further experimental validation in the near future will be necessary to confirm our findings.

Cell surface fluctuations regulate early embryonic lineage sorting.

In development, lineage segregation is coordinated in time and space. An important example is the mammalian inner cell mass, in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the fetus). While the molecular requirements have been well studied, the physical mechanisms determining spatial segregation between EPI and PrE remain elusive. Here, we investigate the mechanical basis of EPI and PrE sorting. We find that rather than the differences in static cell surface mechanical parameters as in classical sorting models, it is the differences in surface fluctuations that robustly ensure physical lineage sorting. These differential surface fluctuations systematically correlate with differential cellular fluidity, which we propose together constitute a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments and modeling, we identify cell surface dynamics as a key factor orchestrating the correct spatial segregation of the founder embryonic lineages.

Cyclocondensation of Anthranilamide with Aldehydes on Gallium-Containing MCM-22 Zeolite Materials.

A gallium-containing MCM-22 (Mobil Composition of Matter No. 22) zeolite material was prepared using a simple hydrothermal method. Fourier transform infrared spectroscopy analysis and powder X-ray diffraction provide evidence of the formation of a pure MCM-22 phase framework and an MWW (MCM-tWenty-tWo) structure. Scanning electron microscopy images showed a uniform spherical shape, interpenetrating the platelet structure and a uniform particle size of approximately 6 µm. 71Ga nuclear magnetic resonance studies confirmed the presence of gallium in both the tetrahedral framework and the octahedral extra-framework environment. From the sorption studies, the presence of strong acidic sites and the microporous nature of the material were evident. The resultant Ga-MCM-22 material showed an excellent isolated yield of 95% in the synthesis of 2,3-dihydroquinazolin-4(1H)-ones by cyclocondensation of anthranilamide with aldehydes in ethanol. The scope of the reaction was further explored by employing various cyclic, aromatic, and aliphatic aldehydes with anthranilamide. The results provide a very good yield (85-95%). A significant advantage of the developed protocol includes high yield, use of a green solvent, and easy removal of the catalyst through filtration within a short reaction time.

A study of self-reported health problems of the people living near railway tracks in Raipur city.

Noise is pervasive in everyday life and can cause both auditory and nonauditory health effects. Noise-induced hearing loss remains highly prevalent in occupational settings. Nonauditory effects of noise can cause tinnitus, headache, auricular plenitude, dizziness, and gastric, visual, sleep, and mood disorders, endocrine imbalance, and cardiovascular disorders. A cross-sectional study among resident above the age of 18 years of the selected urban slum near railway track of Raipur City with a sample size of 400 was conducted. 23.0% of the study subjects responded of facing auditory fatigue, followed by 11.5% of the study subjects reported of hearing loss, 6% of the study participants perceived that the surrounding noise led to an increase in their blood pressure. Loss of sleep/insomnia was reported by 6% of resident in our study. Health effects of environmental noise are manifold, serious and, because of the widespread exposure, very prevalent. These factors stress the need to regulate and reduce environmental noise exposure.

Small-scale demixing in confluent biological tissues.

Surface tension governed by differential adhesion can drive fluid particle mixtures to sort into separate regions, i.e., demix. Does the same phenomenon occur in confluent biological tissues? We begin to answer this question for epithelial monolayers with a combination of theory via a vertex model and experiments on keratinocyte monolayers. Vertex models are distinct from particle models in that the interactions between the cells are shape-based, as opposed to distance-dependent. We investigate whether a disparity in cell shape or size alone is sufficient to drive demixing in bidisperse vertex model fluid mixtures. Surprisingly, we observe that both types of bidisperse systems robustly mix on large lengthscales. On the other hand, shape disparity generates slight demixing over a few cell diameters, a phenomenon we term micro-demixing. This result can be understood by examining the differential energy barriers for neighbor exchanges (T1 transitions). Experiments with mixtures of wild-type and E-cadherin-deficient keratinocytes on a substrate are consistent with the predicted phenomenon of micro-demixing, which biology may exploit to create subtle patterning. The robustness of mixing at large scales, however, suggests that despite some differences in cell shape and size, progenitor cells can readily mix throughout a developing tissue until acquiring means of recognizing cells of different types.

Linear and nonlinear mechanical responses can be quite different in models for biological tissues.

The fluidity of biological tissues - whether cells can change neighbors and rearrange - is important for their function. In traditional materials, researchers have used linear response functions, such as the shear modulus, to accurately predict whether a material will behave as a fluid. Similarly, in disordered 2D vertex models for confluent biological tissues, the shear modulus becomes zero precisely when the cells can change neighbors and the tissue fluidizes, at a critical value of control parameter s0* = 3.81. However, the ordered ground states of 2D vertex models become linearly unstable at a lower value of control parameter (3.72), suggesting that there may be a decoupling between linear and nonlinear response. We demonstrate that the linear response does not correctly predict the nonlinear behavior in these systems: when the control parameter is between 3.72 and 3.81, cells cannot freely change neighbors even though the shear modulus is zero. These results highlight that the linear response of vertex models should not be expected to generically predict their rheology. We develop a simple geometric ansatz that correctly predicts the nonlinear response, which may serve as a framework for making nonlinear predictions in other vertex-like models.

Bioisosteric Replacement of Amide Group with 1,2,3-Triazoles in Acetaminophen Addresses Reactive Oxygen Species-Mediated Hepatotoxic Insult in Wistar Albino Rats.

Acetaminophen (AP) is a popularly recommended over-the-counter analgesic-antipyretic in clinical use. However, the drug is handicapped by the occurrence of hepatotoxic insult following acute ingestion. Consequently, AP-induced hepatotoxicity is often implicated in accidental or suicidal overdose. In the current study, we investigated the potential of bioisosteric replacement of amide in AP with 1,2,3-triazoles in curbing AP-induced hepatotoxicity. The therapeutic utility of synthesized bioisosteres was established by careful tailoring and optimization of the synthetic methodology along with detailed toxicological testing of pharmacologically potent acetaminophen-triazole derivatives (APTDs). Along the same lines, we herein report a series of 17 novel APTDs synthesized via aromatic substitution using sodium azide, l-proline, and copper iodide followed by click reaction with substituted alkynes using copper sulfate and sodium ascorbate. Pharmacological evaluation of synthesized APTDs revealed that, out of the series of 17 compounds, 5a and 5e were found to be most efficacious in exerting anti-inflammatory, analgesic, and antipyretic activity in an animal model. Further toxicity studies documented that, in both acute and sub-acute toxicology, AP administration caused significant hepatotoxicity, which was found to be a consequence of ROS-mediated oxidative stress. Potent APTDs (5a and 5e), on the other hand, revealed no adverse event in both acute and sub-toxicological analyses. Median lethal dose (LD50) and no observed adverse effect level (NOAEL) values for 5a and 5e were found to be >1000 mg/kg and 2000 mg/kg, respectively. The human equivalent dose, defining the maximum safe concentration of a compound in a human's physiology, was found to be 27.68 mg/kg for the most potent APTDs (5a and 5e). Thus, it can be concluded that triazole incorporation into AP nucleus produced conjugates devoid of hepatotoxic manifestations, having the added advantage of anti-inflammatory efficacy along with analgesic and antipyretic potency.

Challenges and Solutions in Implementing Hearing Screening Program in India.

Hearing is the key to learning spoken language, performing academically, and engaging socially for children. Degree of hearing loss quantifies the hearing ability from mild to profound, based on the audiometric findings for an individual across certain frequencies or pitches. Early identification and appropriate intervention is the prime need. A probable strategy is to ensure that every newborn is screened for possible hearing loss at the birth in the hospital. In India, hearing screening facility is mostly available to newborns brought into tertiary hospitals. Some of the key issues in the implementation of the program identified are lack of human resources, inadequate infrastructure, equipment-related shortcomings, and low priority for hearing impairment (HI) prevention. The Government of India initiated efforts toward prevention and control of HI, i.e., National Program for Prevention and Control of deafness and Rashtriya Bal Swasthya Karyakram which are significant milestones in the implementation of systematic nationwide hearing screening programs.

Synthesis, Pharmacological and Toxicological Screening of Penicillin-Triazole Conjugates (PNTCs).

A series of hybrid antimicrobial compounds were prepared by carboxylic acid protection of 6-aminopenicillanic acid using benzyl alcohol and thionyl chloride succeeded by azide displacement using trifluoromethanesulfonyl azide in dichloromethane. The azide thus formed was reacted with substituted alkynes to furnish benzyl-protected penicillin-triazole conjugates. Benzyl deprotection of the conjugates resulted in furnishing PNTCs under water methanol mixture using Pd/C as a catalyst. The PNTCs (7a-j) formed were screened for in vitro antibacterial potency against pathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes and antifungal potency against Candida albicans, Aspergillus niger, and Aspergillus clavatus. Further antimicrobial evaluation revealed compounds 7c, 7d, 7e, 7g, and 7i to be the most compounds of the series with minimum inhibitory concentration value for antibacterial in the range 0.5-50 µg/mL and for antifungal in the range 9-300 µg/mL. Toxicological analysis documented for compounds 7c, 7d, 7e, 7g, and 7i revealed compound 7i to be the most promising member of the series with 1000 and 500 mg/kg LD50, and no-observed-adverse-effect level to facilitate future clinical studies of the same.

Central recruitment in individual with auditory neuropathy.

Auditory neuropathy (AN) describes patients with dysfunction of the auditory nerve in the presence of preserved cochlear outer hair-cell receptor functions in presence of normal otoacoustic emissions and/or cochlear microphonics. In individuals with auditory neuropathy speech are disproportionate to their hearing sensitivity and reported to be dependent on cortical evoked potentials. In individuals with AN, who have normal cortical potentials have better speech identification scores when compared to those with abnormal cortical potentials reflect relation between the cortical potentials and the speech identification scores. One group comparison research design was used for present study. The purpose of the study was to compare shift in latency of LLR peaks at different sensation level in subjects with auditory neuropathy and age matched normal individuals. 6 subjects (11 ears) diagnosed as having auditory neuropathy and 6 subjects (12 ears) with normal hearing Sensitivity participated for the study. Pure tone audiometry, immittance, reflexometry and otoacoustic emissions were administered. ABR was recorded for all the subjects at a repetition rate of 11.1 at an intensity of 90 dB nHL. LLR was carried out at different intensity levels for/da/speech stimulus at an intensity of 90 dB nHL. Latency of N1 and P2 of LLR was calculated at different sensation levels for both the groups. Descriptive analysis was carried out to find out the mean and standard deviation for latency of N1 and P2 for both, AN and normal hearing group. There was delay in latency of N1 and P2 for individuals with auditory neuropathy.