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D-penicillamine (PA) is the primary chelator of choice to treat Wilson disease (WD). There are limitations in obtaining comprehensive data on PA metabolites in biological specimens by conventional approaches. Hence, the aim of the present was to identify the major hepatic PA metabolites and draw clear conclusions of the drug's xenobiotic in WD. Urine samples were collected from children with hepatic WD (n = 63, aged 14.8 ± 4 years) 5 h after PA administration (16.3 ± 3.8 mg/kg/day) and age-matched healthy volunteers comprised as controls (n = 30). High-resolution 800 MHz nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry was applied to reveal unambiguous appraisals of different excretory by-products of PA metabolism. Four new products comprising penicillamine disulphide (PD), penicillamine cysteine disulphide (PCD), S-methyl penicillamine (SMP), and N-acetyl penicillamine (NAP) of PA xenobiotic metabolites were identified using high-resolution NMR spectroscopy. Quantitative levels of PCD and SMP were approximately three-fold higher than those of PD and NAP, respectively. High-resolution NMR identifies the major PA metabolites with certainty. Reduction, sulfation, and methylation are the predominant pathways of PA metabolism. There is a potential application for assessing therapeutic monitoring of chelation in hepatic WD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Total anomalous pulmonary venous connection (TAPVC), with an intrapulmonary segment (IPV), a meandering abnormally located confluence and obligatory drainage of one lung into the other before entering the systemic circulation, is a rare anomaly and we term it as the meandering intrapulmonary TAPVC (MITAPVC)., Material and Methods: We report five patients with an unusual variation of the TAPVC channel. A review of literature was done to identify this association of TAPVC with an intrapulmonary vein and absence of a confluence in its usual location., Results: In our study, 4 patients with neo-confluence creation had excellent outcome while one with partial correction required catheter-based intervention, but succumbed to persistent pulmonary hypertension refractory to therapy. A literature search showed 25 additional such patients. Two groups were noted, one with isolated lesions ( N  = 16) and the other with heterotaxy or complex intracardiac lesions ( N  = 14). Of the 20 surgical interventions, only 12 survived, most of them in the isolated group ( N  = 10). Mortality was due to incomplete surgery (4/4), inappropriate surgery (3/3), and complete and appropriate surgery (1/11) respectively., Conclusion: The MITAPVC is often associated with heterotaxy and complex lesions. However, the isolated version is being increasingly recognised. Non-recognition or inappropriate surgical correction of MITAPVC is associated with fatal outcomes. Evaluation by a computerised tomography (CT) scan, meticulous dissection and demonstration of the entire channel, creation of a neo-confluence and appropriate palliation for the heterotaxy is the key to ensure good outcome. This is not a new entity, but deserves a separate subclassification under TAPVC., Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-021-01290-2., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Association of Cardiovascular-Thoracic Surgeons 2022.)

Background: Surgical correction of total anomalous pulmonary venous connection (TAPVC) remains associated with significant mortality despite advances in intra-operative and postoperative management. We retrospectively analyzed 492 consecutive TAPVC patients with biventricular physiology, who were operated at our centre, with regard to predictors of mortality, morbidity, and intermediate-term outcomes., Materials and Methods: A total of 492 TAPVC patients with biventricular physiology were operated at our centre from August 2009 to November 2019. Their medical records were reviewed and were followed up during March-April 2020 for any symptoms of cardiac disease., Results: Of 492, 302 (61.38%) were healthy at follow-up, 29 (5.89%) had postoperative mortality, 23 (4.67%) had mortality during the follow-up period, and 138 (28.05%) were lost to follow up. Age <1 month and weight <2.5 kg were associated with higher mortality with odds ratios (OR) of 6.37 and 5.56, respectively. There was no difference in mortality in different types of TAPVC. Obstructed TAPVC was associated with higher mortality with OR of 3.05. Acute kidney injury requiring peritoneal dialysis and sepsis were associated with higher mortality with ORs of 10.17 and 3.29, respectively. All follow-up mortality occurred in <1 year from the index operation. Anastomotic gradients were significantly higher in patients who died., Conclusions: Although peri-operative TAPVC mortality has reduced, mortality on follow-up continues to occur and is partly due to the obstruction of pulmonary venous pathway. Meticulous follow-up holds the key in further reducing the mortality. Larger studies are needed for the identification of risk factors for pulmonary venous obstruction and its preventive strategies., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Pediatric Cardiology.)

Cyclin-dependent kinase 2 (CDK2) is an established target protein for therapeutic intervention in various diseases, including cancer. Reported inhibitors of CDK2 target the ATP-binding pocket to inhibit the kinase activity. Many small molecule CDK2 inhibitors have been discovered, and their crystal structure with CDK2 or CDK2-cyclin A complex has been published. NU6140 is a CDK2 inhibitor with moderate potency and selectivity. Herein, we report the cocrystal structure determination of NU6140 in complex with CDK2 and confirmation of the binding using various biophysical methods. Our data show that NU6140 binds to CDK2 with a Kd of 800 nM as determined by SPR and stabilizes the protein against thermal denaturation (ΔT m -5°C). The cocrystal structure determined in our study shows that NU6140 binds in the ATP-binding pocket as expected for this class of compounds and interacts with Leu83 and Glu81 with regular hydrogen bonds and with Asp145 via water-mediated H-bond. Based on these data, we propose structural modifications of NU6140 to introduce new interactions with CDK2 that can improve its potency while retaining the selectivity., (© 2021 John Wiley & Sons Ltd.)

In this article, a zirconia-based nano-catalyst (Nano-ZrO 2 ), with intermolecular C-N bond formation for the synthesis of various benzimidazole-fused heterocycles in a concise method is reported. The robustness of this reaction is demonstrated by the synthesis of a series of benzimidazole drugs in a one-pot method. All synthesized materials were characterized using 1 HNMR, 13 CNMR, and LC-MS spectroscopy as well as microanalysis data. Furthermore, the synthesis of nano-ZrO 2 was processed using a standard hydrothermal technique in pure form. The crystal structure of nano-ZrO 2 and phase purity were studied, and the crystallite size was calculated from XRD analysis using the Debye-Scherrer equation. Furthermore, the antimicrobial activity of the synthesized benzimidazole drugs was evaluated in terms of Gram-positive, Gram-negative, and antifungal activity, and the results were satisfactory.

Context and Aim: The inaccuracies in clinical examination have been well documented, while advanced imaging modalities, including computed tomography and magnetic resonance imaging (MRI), have been shown to have superior diagnostic accuracy in detecting occult and nodal metastasis. The aim of the present study was to identify as well as evaluate the inaccuracies in clinical examination and of clinical diagnostic criteria in known cases of oral squamous cell carcinomas (OSCCs) with the help of MRI., Materials and Methods: A total of 24 patients attending as outpatients were included in the study, while clinically diagnosed and histopathologically proven cases of OSCC were examined clinically and then subjected to advanced imaging with the help of MRI., Statistical Analysis Used: Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA), while paired t -test was performed for evaluating the size of tumor and lymph node recorded on clinical and imaging findings. A P < 0.05 was considered statistically significant., Results: Detection of tumor size and lymph node metastasis was found to be higher in case of MRI than when accomplished by clinical staging alone, while paired t -test values for difference in results were found to be statistically significant ( P < 0.05)., Conclusions: The present study showed that clinical diagnostic criteria alone were not sufficient and reliable for detecting metastatic lymphadenopathy, highlighting the significance of advanced imaging modalities such as MRI for an efficient preoperative diagnostic workup, as well a tool for planning treatment in patients with OSCCs., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Carcinogenesis.)

Paediatric facial fractures are relatively rare. The inherent elasticity of the bones with more of the cartilage than that of the mineralised bone accounts for this. The principles involved in the management of facial fractures are the same irrespective of the age of the patient; however, in children, the techniques used are necessarily modified by certain anatomical, physiological, psychological and feeding factors related to childhood and the parents. In an attempt to keep the treatment and fixation technique simple, the case, presented here, describes the management of a mandibular parasymphyseal fracture in a 16-month-old child with the use of a prefabricated adaptable surgical splint., Competing Interests: None

Background: Locoregional recurrence rates following parotidectomy for cancer remain as high as 20-30%. The auriculotemporal nerve (ATN) may allow parotid cancers to spread from the facial nerve (FN) toward the skull base, causing local recurrence., Methods: Retrospective review of 173 parotidectomies for malignancy. Preoperative and post-recurrence imaging were reviewed by a neuroradiologist for signs of tumor adjacent to the ATN., Results: Clinical and imaging signs of possible ATN involvement correlated with FN weakness and sacrifice. Eight patients had pathologically confirmed tumor from the ATN or V3. Forty-four percent of local recurrences had post-recurrence imaging showing tumor along the course of the ATN. Locoregional failure along the ATN was also associated with preoperative FN weakness, intraoperative FN sacrifice, and failure to complete recommended adjuvant therapy., Conclusions: Parotid cancers may invade the FN and spread to the skull base via the ATN. If not appropriately managed, this may lead to local recurrence., (© 2020 Wiley Periodicals LLC.)

Acinetobacter baumannii is an opportunistic Gram-negative bacterial pathogen, associated mostly with hospital-acquired infections. The emergence of drug resistance strains made it necessary to explore new pathways for the development of more effective antibiotics. Enoyl CoA reductase (FabI), a key enzyme in the fatty acid biosynthesis (FAS) pathway, has emerged as a potential target for antibacterial drug development. Earlier reports show that the lead SaFabI inhibitor AFN-1252 can inhibit FabI from other organisms including Escherichia coli and Burkholderia pseudomallei, but with differential potency. In the present work, we show that AFN-1252 is a moderate inhibitor of AbFabI with an IC 50 of 216 nM. AFN-1252 stabilized AbFabI with a 4.2°C increase in the melting temperature (T m ) and, interestingly, the stabilization effect was significantly increased in presence of the cofactor NADH (∆T m  = 17°C), suggesting the formation of a ternary complex AbFabI: AFN-1252: NADH. X-ray crystallography studies of AbFabI co-crystalized with AFN-1252 and NADH confirmed the ternary complex formation. The critical interactions of AFN-1252 with AbFabI and NADH identified from the co-crystal structure may facilitate the design and development of new drugs against A. baumannii infections by targeting the FAS pathway., (© 2020 John Wiley & Sons A/S.)

Aims: A series of six 4-benzylidene-2-((1-phenyl-3,4-dihydro isoquinoline-2(1H)-yl)methyloxazol- 5(4H)-one derivatives were synthesized by condensation of substituted aryl aldehydes with 2-(2-(1-phenyl-3,4- dihydro isoquinoline-2(1H)-acetamido)acetic acid in the presence of sodium acetate, acetic anhydride and zinc oxide as catalysts., Background: Novel Synthesis of 4-Benzylidene-2-((1-phenyl-3,4-dihy droisoquinoline-2(1H)-yl)methyl)oxazol- 5(4H)-one derivatives using 1,2,3,Tetrahydroisoquinoline and their antimicrobial activity., Objective: The title compounds can be synthesized from 1,2,3,4-tetrahydroisoquinoline., Methods: The target molecules, i.e., 4-benzylidene-2-((1-phenyl-3, 4-dihydro isoquinoline-2(1H)-yl) methyl) oxazol-5(4H)-one derivatives (8a-8f) have been synthesized from 1,2,3,4-tetrahydroisoquinoline which was prepared from benzoic acid in few steps., Results: All the six compounds were evaluated based on advanced spectral data (1H NMR, 13C NMR & LCMS), and the chemical structures of all compounds were determined by elemental analysis., Conclusion: Antibacterial activity of the derivatives was examined for the synthesized compounds and results indicate that compound with bromine substitution has a good activity profile., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose of Review: To review current, effective and more popular techniques for scleral fixation of intraocular lens (IOLs) and IOL-capsular bag complex., Recent Findings: Scleral fixation of IOLs became popular, originally with sutured scleral fixated IOLs and later the Scharioth technique of intrascleral haptic fixation. This was further developed as the Glued IOL technique which enjoys widespread adoption all over the world. Recently the Yamane technique has also become popular and is being widely adopted as well., Summary: Scleral fixated IOLs have evolved in the last 2 decades with technical modifications, extended indications and improvised instrumentation. Though sutured and sutureless techniques have been growing equally, the sutureless scleral fixation techniques have attracted special interest. Reduced suture-related complications, technical ease and high-quality functional outcomes may be possible reasons. Sutureless capsular bag fixation also has distinct advantages.

Objective: To determine the diagnostic accuracy of fine-needle aspiration (FNA) and imaging modalities for low-grade mucoepidermoid carcinoma (MEC) of the parotid gland., Methods: Retrospective chart review of patients diagnosed with low-grade MEC of the parotid gland following surgical excision between January 2010 and June 2018. Imaging from patients with MEC were randomly mixed with imaging from patients with benign pathology and reviewed in a blinded fashion. Main outcome measure was sensitivity., Results: A total of 24 patients were confirmed to have had low-grade MEC on final pathology, with a total of 31 FNAs performed between them. Twelve of 31 FNAs were positive for low-grade MEC, with a sensitivity of 39%. A total of 27 imaging studies were reviewed, which included 16 patients with low-grade MEC and 11 patients with benign pathology. Of these 27 imaging studies, 10 were declared indeterminate. Of the remaining 17 imaging studies, 13 were reviewed as malignant (11 true positive and 2 false positive) and 4 as benign (4 true negative). Overall magnetic resonance imaging (MRI) sensitivity for low-grade MEC was 100% (9/9) with 95% CI (0.66-1.0) when considering indeterminate results as positive for malignancy., Conclusion: This study reaffirms that for low-grade MEC, sensitivity of FNA is poor. MRI provides an important diagnostic tool in the evaluation of salivary gland neoplasms, due to its increased sensitivity for low-grade MEC when considering indeterminate results as positive. This provides confidence in the diagnosis of benign tumors and allows appropriate counseling of all options to the patient, including observation. Imaging and low threshold of excision should be considered despite an inflammatory or benign FNA.

Purpose: To determine the feasibility of using telemedicine consultations in the evaluation of recovered donor corneas for transplant suitability., Methods: This study aims to establish and test the minimum imaging requirements for telemedical consultations of corneal tissue by remote eye bank medical directors. Digital images from the slit lamp, optical coherence tomography, and/or specular microscope were assembled into telemedical consults and emailed to 4 eye bank medical directors (M.A.T., J.W., C.S.S., N.K.R.). Feedback on the minimum image requirements for each corneal finding was collected. After establishing a standardized imaging and presentation protocol, test cases were presented to the medical directors to examine the validity of these remote consults. To establish a benchmark for the study's parameters, one medical director (J.W.) examined each case in person after his initial remote review. Examiners were masked to each other's responses., Results: Minimum image requirements for determination of corneal findings were defined and were specific to each anatomic layer of the cornea (epithelial, stromal, or endothelial). Using a defined set of digital images for a set of common corneal findings, the rate of agreement between remote evaluators, eye bank staff, and the in-person evaluator was 100% (11 of 11 examples). For ambiguous test cases, remote evaluators agreed on 80% of the cases (4 of 5)., Conclusions: Results from this pilot study suggest that telemedical review of corneal tissue using high-quality digital images may be adequate for accurate identification of specific corneal findings commonly encountered by eye banks.

Computer-based assessment of many cognitive processes (eg, anticipatory and response readiness processes) requires the use of invariant stimulus display times (SDT) and intertrial intervals (ITI). Although designs with invariant SDTs and ITIs have been used in functional magnetic resonance imaging (fMRI) research, such designs are problematic for fMRI studies because of collinearity issues. This study examined regressor modulation with trial-level reaction times (RT) as a method for improving signal detection in a go / no-go task with invariant SDTs and ITIs. The effects of modulating the go regressor were evaluated with respect to the detection of BOLD signal-change for the no-go condition. BOLD signal-change to no-go stimuli was examined when the go regressor was based on a (a) canonical hemodynamic response function (HRF), (b) RT-based amplitude-modulated (AM) HRF, and (c) RT-based amplitude and duration modulated (A&DM) HRF. Reaction time-based modulation reduced the collinearity between the go and no-go regressors, with A&DM producing the greatest reductions in correlations between the regressors, and greater reductions in the correlations between regressors were associated with longer mean RTs and greater RT variability. Reaction time-based modulation increased statistical power for detecting group-level no-go BOLD signal-change across a broad set of brain regions. The findings show the efficacy of using regressor modulation to increase power in detecting BOLD signal-change in fMRI studies in which circumstances dictate the use of temporally invariant stimulus presentations., Competing Interests: Declaration Of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Using diffusion tensor imaging (DTI), we assessed the relationship of white matter integrity and performance on the Boston Naming Test (BNT) in a group of retired professional football players and a control group. We examined correlations between fractional anisotropy (FA) and mean diffusivity (MD) with BNT T-scores in an unbiased voxelwise analysis processed with tract-based spatial statistics (TBSS). We also analyzed the DTI data by grouping voxels together as white matter tracts and testing each tract's association with BNT T-scores. Significant voxelwise correlations between FA and BNT performance were only seen in the retired football players (p < 0.02). Two tracts had mean FA values that significantly correlated with BNT performance: forceps minor and forceps major. White matter integrity is important for distributed cognitive processes, and disruption correlates with diminished performance in athletes exposed to concussive and subconcussive brain injuries, but not in controls without such exposure., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Background & Objectives: Child-Pugh score (CPS) is a widely used prognostic marker in cases of cirrhosis and pulmonary arterial hypertension (PAH). However, the role of this score in the quantification of severity of PAH is not well studied. In mild cases, echocardiography is more sensitive. This study was done to assess the association between echocardiography and severity of cirrhosis using CPS., Methods: A cross-sectional study was done from April to June 2014 in 42 patients with cirrhosis using a pre-tested semi-structured interview schedule., Results: There was no significant association between echocardiographic changes and CPS in patients with liver cirrhosis., Interpretation & Conclusions: Advising an echocardiographic evaluation may prove beneficial in patients of Child-Pugh Grades B and C. However, more extensive studies are required to confirm the same.

Quinoa is recognized as a crop of great value in terms of tolerance to abiotic stresses and there is growing interest to introduce it in marginal agricultural production systems worldwide. Also, quinoa is one of the most nutritious food crops currently known and the nutritive properties of the crop are seen as a mean to fight malnutrition globally. Various quinoa cultivars have been screened for tolerance to salinity, water-use efficiency and nutritional quality and the positive attributes found in them have created even wider global interest in its cultivation. This paper summarizes 15 years of studies on assessing the potential for introducing the crop in a few countries of the Middle East and North Africa (MENA) and Central Asia regions and describes the key constraints for scaling-up the production under marginal growing conditions in the newly introduced countries.

Background: Coronal incision is a popular and versatile surgical approach to the anterior cranial vault and upper and middle third facial skeleton. The flap itself permits widespread exposure of the fractures in this region. The bicoronal flap was first described by Hartley and Kenyon (neurosurgeons) to gain access to the anterior cranium in 1907. It extension as an access flap to the upper and lateral aspect of the face was pioneered by Tessier (1971). Esthetically, it is pleasing as the surgical scar is hidden within the hair., Aims: To evaluate the versatility of coronal incision using various modifications advocated in incision, exposure to fractured site, and closure of flap in treating the upper and middle third facial fractures., Materials and Methods: A total of ten patients diagnosed with upper and middle third facial fractures requiring open reduction and internal fixation/correction of contour defect were selected after preoperative clinical and radiographic (computed tomography scan) evaluation. All the cases were operated by coronal approach to gain the access to the fracture/defect site for reduction/correction of the defect. Advantages and complication are evaluated., Results: Excellent access and anatomical reduction by this approach with least number of complications; if it is performed with healthy knowledge of anatomy of the scalp and temporal region. Certain minimal complications have also been noted using various modifications used in the procedure., Conclusion: Despite of prolonged surgical time for the exposure, it is very advantages in treating upper and middle third facial fractures due to wide access and discreet scar (minimal)., Competing Interests: There are no conflicts of interest.

Background: This study was carried out to evaluate the effect of two commercially available chemical disinfectants namely sodium hypochlorite and glutaraldehyde and a surface wetting agent on the wettability of three high precision elastomeric impression materials, addition silicone, condensation silicone and polyether., Materials and Methods: Three different types of elastomeric impression materials commonly used in prosthodontic practice were selected. The glutaraldehyde and sodium hypochloride solutions were employed to disinfect the impressions made with the above-mentioned elastomeric impression materials. True Blue surface wetting agent was selected. GBX contact angle analyzer was used to measure advancing and receding contact angle., Results: The results of this study have demonstrated that the polyether impression material was the most hydrophilic of all the materials, followed by hydrophilic addition silicone. Condensation silicone was least hydrophilic. All materials showed improvement in the wettability when a topical surfactant was used., Conclusion: The short term disinfection of the three elastomeric impression materials does not affect the wettability of these impression materials.