Application of in-silico drug discovery techniques to discover a novel hit for target-specific inhibition of SARS-CoV-2 Mpro's revealed allosteric binding with MAO-B receptor: A theoretical study to find a cure for post-covid neurological disorder.

Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection. In light of this situation, we have employed a variety of computational to develop suitable QSAR model using PyDescriptor and genetic algorithm-multilinear regression (GA-MLR) models (R2 = 0.800-793, Q2LOO = 0.734-0.727, and so on) on the data set of 106 molecules whose anti-SARS-CoV-2 activity was empirically determined. QSAR models generated follow OECD standards and are predictive. QSAR model descriptors were also observed in x-ray-resolved structures. After developing a QSAR model, we did a QSAR-based virtual screening on an in-house database of 200 compounds and found a potential hit molecule. The new hit's docking score (-8.208 kcal/mol) and PIC50 (7.85 M) demonstrated a significant affinity for SARS-CoV-2's main protease. Based on post-covid neurodegenerative episodes in Alzheimer's and Parkinson's-like disorders and MAO-B's role in neurodegeneration, the initially disclosed hit for the SARS-CoV-2 main protease was repurposed against the MAO-B receptor using receptor-based molecular docking, which yielded a docking score of -12.0 kcal/mol. This shows that the compound that inhibits SARS-CoV-2's primary protease may bind allosterically to the MAO-B receptor. We then did molecular dynamic simulations and MMGBSA tests to confirm molecular docking analyses and quantify binding free energy. The drug-receptor complex was stable during the 150-ns MD simulation. The first computational effort to show in-silico inhibition of SARS-CoV-2 Mpro and allosteric interaction of novel inhibitors with MAO-B in post-covid neurodegenerative symptoms and other disorders. The current study seeks a novel compound that inhibits SAR's COV-2 Mpro and perhaps binds MAO-B allosterically. Thus, this study will enable scientists design a new SARS-CoV-2 Mpro that inhibits the MAO-B receptor to treat post-covid neurological illness.

Ultra-Wideband Microwave Imaging System for Root Phenotyping.

The roots are a vital organ for plant growth and health. The opaque surrounding environment of the roots and the complicated growth process means that in situ and non-destructive root phenotyping face great challenges, which thus spur great research interests. The existing methods for root phenotyping are either unable to provide high-precision and high accuracy in situ detection, or they change the surrounding root environment and are destructive to root growth and health. Thus,we propose and develop an ultra-wideband microwave scanning method that uses time reversal to achieve in situ root phenotyping nondestructively. To verify the method's feasibility, we studied an electromagnetic numerical model that simulates the transmission signal of two ultra-wideband microwave antennas. The simulated signal of roots with different shapes shows the proposed system's capability to measure the root size in the soil. Experimental validations were conducted considering three sets of measurements with different sizes, numbers and locations, and the experimental results indicate that the developed imaging system was able to differentiate root sizes and numbers with high contrast. The reconstruction from both simulations and experimental measurements provided accurate size estimation of the carrots in the soil, which indicates the system's potential for root imaging.

First Comprehensive Report of Clinicopathological Profile of Breast Cancer from Bihar, India.

Only a few countries of the world have a population more than Bihar, but due to the lack of a cancer registry, authentic research, and publications, data regarding the clinicopathological characteristics of breast cancer patients from this state are scarce. The present study was aimed to report the clinicopathological characteristics of breast cancer patients at a tertiary care center in Bihar, India. This is a retrospective review of a prospectively maintained database of patients of breast cancer treated between January-2018 and March-2020. One hundred fifteen patients with breast carcinoma were included of which 112 (97.4%) were women. The mean age was 47.28 ± 11.62 years and 54.5% of women were postmenopausal. Most patients had a clinical stage of II or III (44.5% each) while 8.7% of patients had stage IV disease. Invasive ductal carcinoma no special type (IDC-NST) was the most common histology (85.2%). The majority of tumors were grade II (55.6%), lymphovascular invasion was seen in 45.6%, and perineural invasion in 18.4%. Estrogen receptor was found in 41.8%, progesterone receptor was positive in 47.3%, and human epidermal growth factor receptor-2 (HER-2/Neu) overexpression was observed in 39.8%. Triple-negative breast cancer was found in 26.2% of patients. The majority underwent mastectomy (71.3%) while breast conservation was done in 26%. All except one patient underwent axillary lymph node dissection for axillary staging. 43.5% patients received neoadjuvant chemotherapy, 52.9% received adjuvant chemotherapy, while 3.5% patients received palliative chemotherapy. The clinicopathological profile of breast cancer patients from Bihar is similar to that reported from other parts of India except for a lower rate of distant metastasis.

A Review of Acoustic Impedance Matching Techniques for Piezoelectric Sensors and Transducers.

The coupling of waves between the piezoelectric generators, detectors, and propagating media is challenging due to mismatch in the acoustic properties. The mismatch leads to the reverberation of waves within the transducer, heating, low signal-to-noise ratio, and signal distortion. Acoustic impedance matching increases the coupling largely. This article presents standard methods to match the acoustic impedance of the piezoelectric sensors, actuators, and transducers with the surrounding wave propagation media. Acoustic matching methods utilizing active and passive materials have been discussed. Special materials such as nanocomposites, metamaterials, and metasurfaces as emerging materials have been presented. Emphasis is placed throughout the article to differentiate the difference between electric and acoustic impedance matching and the relation between the two. Comparison of various techniques is made with the discussion on capabilities, advantages, and disadvantages. Acoustic impedance matching for specific and uncommon applications has also been covered.

Convergence excess consecutive esotropia associated with 0.01% atropine eye drops usage in patients operated for intermittent exotropia.

To report convergence excess esotropia (CEET) following 0.01% atropine eye drops (Low dose atropine [LDA]). Children who developed CEET that resolved promptly after discontinuation of LDA are described. Three myopes aged 5.3 ± 1.2 years and mean sphere -4.5D were included. All were operated for intermittent exotropia earlier. Mean esotropia was +28.3PD for near and 10.6PD for distance. LDA induced high AC/A ratio and fusion normalized in 3 weeks after discontinuation of LDA. LDA should be used with caution in patients with esophoria or previously operated for intermittent exotropia. Any evidence of the emergence of a CEET should warrant discontinuation of LDA.

Intracystic papillary carcinoma of the male breast: Dilemmas in diagnosis and management.

Intracystic papillary carcinoma (IPC) is a rare malignancy of the breast which is usually found in postmenopausal women. It is still rarer in males and may present with signs of a benign cystic lump. It is sub-classified into three equally prevalent groups considering treatment strategies: intracystic papillary carcinoma alone, intracystic papillary carcinoma with ductal carcinoma in-situ, and those with evidence of invasion. Even if a preoperative diagnosis is achieved, there are no specific guidelines for the treatment of IPC. Treatment modalities including the extent of surgical excision, lymph node dissection, radiation, and chemotherapy are determined by the grade and size of the lesion and sub-types. However, several reports and studies showed good prognosis with conservative surgery without axillary dissection in IPC not associated with carcinoma in situ or micro-invasion. We present a 40 years old male patient with IPC who was managed by modified radical mastectomy and adjuvant hormone therapy. A brief review of the literature and clinical characteristics, pathology, and treatment of IPC are discussed.

Estimation Dynamic Distance Direct Ophthalmoscopy (eDDDO): A novel, objective method for the quantitative assessment of accommodation in young children.

Purpose: To describe estimation dynamic distance direct ophthalmoscopy (eDDDO) and compare it with the monocular estimation method of dynamic retinoscopy (eDR) for the assessment of accommodation in children. Methods: In this prospective observational cohort study, an ophthalmologist performed eDDDO followed by eDR in children with normal eyes, and then under the partial effects of cyclopentolate and tropicamide to assess performance of eDDDO with eDR under the condition of pharmacologically induced accommodation failure. Only one eye of each child was recruited in the study. To study the inter-observer variation, two masked pediatric ophthalmology fellows performed eDDDO in the similar manner. Results: For the comparison of eDDDO with eDR, 60 eyes of 60 patients were recruited. The mean age of the patients was 10.4 years. The mean accommodation on eDDDO was 3.0D, 5.1D, 9.8D, and 11.3D at 40 cm, 25 cm, 10 cm, and 8 cm, respectively and 3.0D, 5.0D, 9.5D, and 11.0D on eDR. The eDDDO overestimated accommodation by a mean 0.17D (95% CL 0-0.48D, P = 0.5). The correlation of eDDDO with eDR was excellent (Pearson r 0.98, T value 76.0). The inter-observer difference with eDDDO was not significant (mean 1D, 95% CL 0-2.6D, P = 0.9) and the correlation between two observers was excellent (Pearson r 0.9, T value 12.7). The eDDDO and eDR were also performed on 12 eyes of 6 children with a mean age of 8.5 years (range 8-12 years) under the partial effect of cyclopentolate and tropicamide, where eDDDO overestimated the accommodation by a mean 0.3D (95% CL 0- 1.2D, P = 0.7) and the correlation was excellent (Pearson r 1.0, T value 45). Conclusion: eDDDO is a simple, reliable, quantitative, and objective technique of accommodation assessment for children. Further studies with larger sample are required to assess its performance in disorders of accommodation affecting younger children and in children with ocular comorbidities.

Allergic reactions to atropine eye drops for retardation of progressive myopia in children.

PURPOSE: To report clinical manifestations of ocular allergy to atropine eye drops used for retardation of progressive myopia in children. METHODS: Myopic children, who developed bothersome itching that subsided promptly after cessation of atropine eye drops, were included. History of systemic or ocular allergy, preexisting ocular conditions, and clinical features of allergy were noted. RESULTS: Six children, age 5-15 years, were included. Four developed allergy to 1% atropine sulfate eye drops and two to 0.01% concentration of atropine sulfate. The onset of allergy was within a month to as late as 4 years after using atropine eye drops. The severity of allergy was higher with 1% concentration. The most common symptoms of atropine allergy were itching and burning. The most common signs were lid swelling and hyperemia. The allergic manifestations promptly reversed with the stoppage of eye drops. Reintroduction was possible in three patients, either by reducing the concentration of atropine or using benzalkonium free formulation. CONCLUSION: Allergy to atropine eye drops in children may develop within a few weeks or after many years of usage. Prompt cessation followed by a reintroduction and continuation of therapy may be possible in few patients.

Efficacy of 1% atropine eye drops in retarding progressive axial myopia in Indian eyes.

PURPOSE: The aim of this study is to assess the efficacy of 1% atropine eye drops for the retardation of progressive axial myopia in Indian eyes. METHODS: This prospective interventional cohort study included children aged 5-16 years. Both the eyes of myopic children with progressive increase of ≥-0.5D sphere/year with the best-corrected vision of ≥6/6 were treated with once a day application of 1% atropine eye drops and progressive addition photogray lenses. The progression of myopia after 1-year follow-up was analyzed. RESULTS: Sixty eyes of thirty myopes were included in the study. The mean age was 10 years and 15 were girls. The mean baseline sphere was -5.2D (-2.5D--13D). Mean duration of follow-up was 23 months (12-36 months). The baseline rate of progression was reduced from -0.6D/year (range -0.5D/year to -3D/year) to -0.2D/year (range 0D/year to -1.5D/year) after atropine therapy. Seventeen patients (57%) had to use the atropine in the daytime to reach the target progression of P = 0.6). The efficacy of atropine drops did not have a correlation with the age of the patients or the magnitude of baseline myopia (Pearson's r = 0). CONCLUSION: 1% atropine eye drops was well tolerated and efficacious for the retardation of progressive myopia in Indian eyes. Effectiveness was better with daytime application. Further studies are necessary to assess the role of 1% atropine in the rapid progressors and patients poorly responding to low-dose atropine.

Optimization of a Diaphragm for a Micro-Shock Tube-Based Drug Delivery Method.

This paper presents the design optimization of diaphragms for a micro-shock tube-based drug delivery device. The function of the diaphragm is to impart the required velocity and direction to the loosely held drug particles on the diaphragm through van der Waals interaction. The finite element model-based studies involved diaphragms made up of copper, brass and aluminium. The study of the influence of material and geometric parameters serves as a vital tool in optimizing the magnitude and direction of velocity distribution on the diaphragm surface. Experiments carried out using a micro-shock tube validate the final deformed shape of the diaphragms determined from the finite element simulation. The diaphragm yields a maximum velocity of 335 m/s for which the maximum deviation of the velocity vector is 0.62°. Drug particles that travel to the destination target tissue are simulated using the estimated velocity distribution and angular deviation. Further, a theoretical model of penetration helps in the prediction of the drug particle penetration in the skin tissue like a target, which is found to be 0.126 mm. The design and calibration procedure of a micro-shock tube device to alter drug particle penetration considering the skin thickness and property are presented.

Ultrasonography for masseter muscle cysticercosis.

Solitary cheek swellings can present a diagnostic dilemma. We managed two children 10 y and 8 y presenting with pain and swelling on one side of cheek for over 15 d and no constitutional symptoms. Sonography showed cysticercosis in both of them. We treated both with steroids and albendazole, with good response.