A cytomics-on-a-chip platform and diagnostic model stratifies risk for oral lichenoid conditions.

OBJECTIVE: A small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation. Distinguishing OLCs from other oral potentially malignant disorders (OPMDs) can help prevent unnecessary concern or testing, but accurate identification by nonexpert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a 'cytomics-on-a-chip' tool and integrated predictive model for aiding the identification of OLCs. STUDY DESIGN: All study subjects underwent both scalpel biopsy for histopathology and brush cytology. A predictive model and OLC Index comprising clinical, demographic, and cytologic features was generated to discriminate between subjects with lichenoid (OLC+) (N = 94) and nonlichenoid (OLC-) (N = 237) histologic features in a population with OPMDs. RESULTS: The OLC Index discriminated OLC+ and OLC- subjects with area under the curve (AUC) of 0.76. Diagnostic accuracy of the OLC Index was not significantly different from expert clinician impressions, with AUC of 0.81 (P = .0704). Percent agreement was comparable across all raters, with 83.4% between expert clinicians and histopathology, 78.3% between OLC Index and expert clinician, and 77.3% between OLC Index and histopathology. CONCLUSIONS: The cytomics-on-a-chip tool and integrated diagnostic model have the potential to facilitate both the triage and diagnosis of patients presenting with OPMDs and OLCs.

Comparison of Ultrasound Versus Ultrasound With Nerve Stimulation-Guided Obturator Nerve Block to Prevent Adductor Spasm in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomized Controlled Study.

Background This study aimed to compare ultrasound versus ultrasound with nerve stimulation-guided obturator nerve block (ONB) for the prevention of adductor spasm in patients undergoing transurethral resection of bladder tumor (TURBT). Methodology This randomized controlled study included 240 adult patients in the age group of 30 to 70 years undergoing TURBT for lateral and posterolateral wall bladder tumors who fulfilled the American Society of Anesthesiologists grade I and II criteria. The patients were divided into two groups: group U (n = 120) included patients who underwent ONB using an ultrasound-guided technique and group UN (n = 120) included patients who underwent ONB using ultrasound with the nerve stimulation technique. Block performance time, adductor jerks/spasms, adductor muscle power, and patient and surgeon satisfaction were compared. A P-value <0.05 was considered statistically significant. Results The mean block performance time in group U was significantly less (4.4 ± 0.82 minutes) than in group UN (6.55 ± 0.37 minutes). Compared to group U, group UN had significantly fewer adductor jerks/spasms during the surgery (7.76% vs. 20.35%, p = 0.006), significantly more surgeon satisfaction (92.24% vs. 79.65%, p = 0.006), significantly more patient satisfaction (92.24% vs. 79.65%, p = 0.006), and comparable complications (excessive bleeding and minor bladder injury) and adductor muscle power after the block (p > 0.05). Conclusions ONB using the nerve stimulation technique under ultrasound guidance has a longer mean block performance time, a higher success rate, and higher surgeon satisfaction than ONB under ultrasound guidance only.

e-Pharmacophore modeling and in silico study of CD147 receptor against SARS-CoV-2 drugs

Coronavirus has left severe health impacts on the human population, globally. Still a significant number of cases are reported daily as no specific medications are available for its effective treatment. The presence of the CD147 receptor (human basigin) on the host cell facilitates the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Therefore, the drugs that efficiently alter the formation of CD147 and spike protein complex could be the right drug candidate to inhibit the replication of SARS-CoV-2. Hence, an e-Pharmacophore model was developed based on the receptor-ligand cavity of CD147 protein which was further mapped against pre-existing drugs of coronavirus disease treatment. A total of seven drugs were found to be suited as pharmacophores out of 11 drugs screened which was further docked with CD147 protein using CDOCKER of Biovia discovery studio. The active site sphere of the prepared protein was 101.44, 87.84, and 97.17 along with the radius being 15.33 and the root-mean-square deviation value obtained was 0.73 Å. The protein minimization energy was calculated to be –30,328.81547 kcal/mol. The docking results showed ritonavir as the best fit as it demonstrated a higher CDOCKER energy (–57.30) with correspond to CDOCKER interaction energy (–53.38). However, authors further suggest in vitro studies to understand the potential activity of the ritonavir.

Optical Coherence Tomography: An Eye Into the Coronary Artery.

Optical coherence tomography (OCT) is slowly but surely gaining a foothold in the hands of interventional cardiologists. Intraluminal and transmural contents of the coronary arteries are no longer elusive to the cardiologist's probing eye. Although the graduation of an interventionalist in imaging techniques right from naked eye angiographies to ultrasound-based coronary sonographies to the modern light-based OCT has been slow, with the increasing regularity of complex coronary cases in practice, such a transition is inevitable. Although intravascular ultrasound (IVUS) due to its robust clinical data has been the preferred imaging modality in recent years, OCT provides a distinct upgrade over it in many imaging and procedural aspects. Better image resolution, accurate estimation of the calcified lesion, and better evaluation of acute and chronic stent failure are the distinct advantages of OCT over IVUS. Despite the obvious imaging advantages of OCT, its clinical impact remains subdued. However, upcoming newer trials and data have been encouraging for expanding the use of OCT to wider indications in clinical utility. During percutaneous coronary intervention (PCI), OCT provides the detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition) required for optimal stent deployment, which is the key to successfully reducing the major adverse cardiovascular event (MACE) and stent-related morbidities. The increasing use of OCT in complex bifurcation stenting involving the left main (LM) is being studied. Also, the traditional pitfalls of OCT, such as additional contrast load for image acquisition and stenting involving the ostial and proximal LM, have also been overcome recently. In this review, we discuss the interpretation of OCT images and its clinical impact on the outcome of procedures along with current barriers to its use and newer paradigms in which OCT is starting to become a promising tool for the interventionalist and what can be expected for the immediate future in the imaging world.

Molecular Dynamics Simulations of Complexation of Am(III) with a Preorganized Dicationic Ligand in an Ionic Liquid.

Preorganized ligands with imidazolium arms have been found to be highly selective in extracting Am(III) into ionic liquids (ILs), but the detailed structure and mechanism of the complexation process in the ionic solvation environment are unclear. Here, we carry out molecular dynamics simulation of the complexation of Am(III) with a preorganized 1,10-phenanthroline-2,9-dicarboxamide complexant (L) functionalized with alkyl chains and imidazolium cations in the butylmethylimidazolium bistriflimide ([BMIM][NTf2]) IL. Both Am:L (1:1) and Am:L2 (1:2) complexes are examined. In the absence of the ligand, Am(III) is found to be coordinated by six NTf2 anions via nine O donors in the first solvation shell. In the Am:L complex, Am(III) is coordinated to the ligand via two O donors and four NTf2 anions via seven O donors in the first coordination shell. In the Am:L2 complex, Am(III) is coordinated to the two ligands via four O donors and four NTf2 anions via five O donors. The imidazolium arms of the ligands play an important role in the secondary solvation environment by attracting NTf2 anions closer to the metal center. As a result, we find that the binding free energy for the second L2+ ligand is twice that for the first L2+ ligand, making the Am:L2 complex significantly more stable than the Am:L complex. This work highlights the multiple factors and tunability in using preorganized ligands with charged functional groups in an ionic solvation environment, which could hold the key to achieving desired selectivity in ion extraction efficiency.

Comparison of Different Ultrasound Parameters for Airway Assessment in Patients Undergoing Surgery under General Anaesthesia.

AIMS: The aim of this study was to evaluate and correlate ultrasound measurement of airway parameters with the Cormack- Lehane (CL) grading observed under direct laryngoscopy for prediction of difficult airway. METHODS: This prospective, observational study was conducted in a tertiary care institute. Ninety-six patients were scheduled for elective surgery under general anaesthesia and tracheal intubation. They were categorised as having easy (CL grades 1, 2a, and 2b) or difficult (CL grades 3a, 3b, and 4) laryngoscopy. The sonographically measured airway parameters included anterior neck soft tissue thickness at vocal cord level (ANS-VC), hyomental distance ratio (HMDr), and tongue volume (TV). These parameters were compared and correlated with the CL grading. The statistical analysis was done using SPSS version 21.0. RESULTS: Difficult laryngoscopy was observed in 17.7% patients. Significant difference was noted in ANS-VC 0.28 6 0.09; 0.39 6 0.12, (P < .0001) and HMDr, 1.2 6 0.09; 1.15 6 0.13, (P » .006) for easy and difficult laryngoscopy, respectively. ANS-VC had a sensitivity of 78.9% and specificity of 71.1% (AUC-0.816) followed by HMDr (AUC-0.713) and TV (AUC-0.608). Combined ultrasound parameters had significantly higher AUC value (0.867). CONCLUSIONS: ANS-VC was the most significant parameter with a value of >0.29 cm being a sensitive predictor of difficult intubation. Combined sonographic parameters (ANS-VC, HMDr, and TV) were better predictors of difficult intubation.

Physiological Effects of N95 FFP and PPE in Healthcare Workers in COVID Intensive Care Unit: A Prospective Cohort Study.

BACKGROUND: Healthcare workers (HCWs) are at increased risk of exposure to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Personal protective equipment (PPE) is mandated for HCWs. However, the physiological effects on the HCWs while working in the protective gear remains unexplored. This study aimed to assess the physiological effects of the prolonged use of PPE on HCWs. MATERIALS AND METHODS: Seventy-five HCWs, aged 18-50 years were enrolled in this prospective, observational, cohort study. The physiological variables [heart rate, oxygen saturation, and perfusion index (PI)] were recorded at the start of duty, 4 hours after wearing N95 filtering facepiece respirator (FFR), pre-donning, and post-doffing. The rating of perceived exertion (RPE) score and modified Borg scale for dyspnea was evaluated. The physiological variables were represented as the mean ± standard deviation. Wilcoxon signed-rank test was used to show any difference in RPE and modified Borg scale for dyspnea. A p value of <0.05 was considered significant. RESULTS: There is a statistically significant difference in the physiological parameters post-doffing compared with baseline: Heart rate (p < 0.001); oxygen saturation (p < 0.001); PI (p < 0.001). RPE score showed increased discomfort with continuous use of N95 FFR. However, exertion increased only marginally. The major adverse effects noted with PPE use were fogging, headache, tiredness, difficulty in breathing, and mask soakage, with a resultant mean duration of donning to be 3.1 hours. CONCLUSION: The use of PPE can result in considerable changes in the physiological variables of healthy HCWs. The side effects may lead to excessive exhaustion and increased tiredness after prolonged shifts in the intensive care unit (ICU) while wearing PPE. HOW TO CITE THIS ARTICLE: Choudhury A, Singh M, Khurana DK, Mustafi SM, Ganapathy U, Kumar A, et al. Physiological Effects of N95 FFP and PPE in Healthcare Workers in COVID Intensive Care Unit: A Prospective Cohort Study. Indian J Crit Care Med 2020;24(12):1169-1173.

Municipal solid waste (MSW): Strategies to improve salt affected soil sustainability: A review.

Salt-induced soil degradation is a serious threat to global agriculture which is responsible for diminished productivity of agro-ecosystems. Irrigation with poor quality water and indiscriminate use of chemical fertilizers to increase crop productivity creates salt accumulation in soil profile thereby reducing crop sustainability. High concentration of salts in soil inhibits plant growth due to low osmotic potential of the soil solution, ion toxicity and imbalance reduces nutrient uptake, crop yields. Low productivity of saline soils is not only due to salt toxicity or excess amounts of soluble salts but also lack of available mineral nutrients especially nitrogen, phosphorus, potassium and soil organic matter. Hence, sustainable management of salt-affected soils are paramount importance to meet the demands of food grain production for an ever-rising population in the world. Recently, municipal solid waste has gained importance as an organic amendment for restoring soil fertility and finally contributing to productivity of salt-affected soils. This paper compares extant waste generation, their properties and standards pertinent to municipal solid waste in different countries and explores the unique recent history in some countries that shows high environmental regard and rapid changes and also suggests policy experiencing from high environmental regard and rapid changes from other countries, so that policy makers can propose new or revise current municipal solid waste standards for salt affected soils. Municipal solid waste compost improves soil biological, physical and chemical properties because of high soil organic matter and lower concentration of pollutants. Therefore, the use of municipal solid waste in salt-affected soils could be an alternative to costly chemical amendments as well as reduce the reliance on chemical fertilizers for increasing productivity of salt-affected soil. The municipal solid wastes significantly improve crop yields. However, further long-term experimental investigations are needed to re-validate the application of municipal solid waste compost in improving physical, chemical and biological properties and to step up organic fertilization use in a wide range of both saline and sodic soils. In future, research should be directed to address these issues globally to minimise ecological disturbances and to set environmental standards, and evaluate the feasibility of the policies in different countries and their impact on socio-economic conditions of local people.

Persistent sexual dysfunction and depression in finasteride users for male pattern hair loss: a serious concern or red herring?

The use of finasteride for the treatment of male pattern hair loss has recently been the focus of media and internet attention for potential irreversible sexual dysfunction and severe depression. The purpose of this study was to perform a critical review of the recent studies reporting prolonged sexual dysfunction and depression with the use of finasteride for the treatment of male pattern hair loss. A literature search was performed using PubMed to review the literature pertaining to any potential adverse effects with the use of finasteride and its treatment of male pattern hair loss. The authors conclude that the reports of potential irreversible sexual dysfunction and severe depression do raise concerns about the safety of finasteride; however, these studies are wrought with significant bias. Therefore, larger, randomized, double blind, controlled trials are warranted to further ascertain the true potential risks or confirm long-term safety profile of finasteride use.

Attenuation of circulatory and airway responses to endotracheal extubation in craniotomies for intracerebral space occupying lesions: Dexmedetomidine versus lignocaine.

OBJECTIVES: The objective of the study is to compare the effect of dexmedetomidine versus lignocaine in attenuation of circulatory and airway responses during endotracheal extubation in craniotomies for intracerebral space occupying lesions (ICSOL). MATERIALS AND METHODS: A total of 50 patients of American Society of Anesthesiologists Grade I and II of either sex, aged 18-50 years undergoing craniotomies for non-vascular ICSOL under general anesthesia were divided into two groups according to drug received. Group D (n = 25) received dexmedetomidine (0.5 mcg/kg) whereas group L (n = 25) received lignocaine (1.5 mg/kg). Both the drugs were given 5 min before the extubation over a period of 60 s. Values for heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), were recorded just before (A0) and 1, 3, 5 (A1, A3, A5) min after the study drug administration, at extubation (E) and 1, 3, 5, 10, 15 min after extubation (E1, E3, E5, E10 and E15). Respiratory rate, oxygen saturation and airway responses like coughing, breath-holding, laryngospasm/bronchospasm were recorded only at extubation (E) and 1, 3, 5, 10, 15 min after extubation (E1, E3, E5, E10, E15). Quality of extubation was recorded with four point scale. After extubation all these patients were also observed for sedation by Ramsey sedation score. RESULTS: Both groups showed a statistically significant increase (D < L) in HR, SBP and DBP during (E) and immediately after extubation (E1) (P < 0.05). Dexmedetomidine (72%) produced a higher degree of sedation (Grade 3) as compare with lignocaine (0%) and with no incidence of coughing or breath holding (P < 0.05). CONCLUSION: Single dose of dexmedetomidine (0.5 mcg/kg) given 5 min before extubation produced significant attenuation of circulatory and airway responses produced during extubation as compared to Lignocaine (1.5 mg/kg) in ICSOL.

The comparative evaluation of intravenous with intramuscular clonidine for suppression of hemodynamic changes in laparoscopic cholecystectomy.

BACKGROUND: Clonidine diminishes stress response by reducing circulating catecholamines and hence increases perioperative circulatory stability in patients undergoing laparoscopic surgeries. The aim of this study was to compare intravenous (IV) clonidine (2 µg/kg) with intramuscular (IM) clonidine (2 µg/kg) for attenuation of stress response in laproscopic surgeries. METHODS: Eighty adult patients classified as ASA physical status I or II, aged between 20 and 60 years undergoing elective cholecystectomy under general anesthesia were enrolled for a prospective, randomized, and double-blind controlled trial. They received either IV clonidine (2 µg/kg) 15 min prior to the scheduled surgery (Group I) or IM clonidine (2 µg/kg) 60-90 min prior to the scheduled surgery (Group II). Hemodynamic variables (Heart rate, systolic (SBP), diastolic (DBP), mean arterial pressure (MAP)), SpO2 and EtCO2 were recorded at specific times - baseline, prior to induction, 1 min after intubation, before CO2, insufflation, after CO2 insufflation at 1,5,10,20,30,45,60 min, after release of CO2, at 1 and 10 minutes after extubation. Secondary outcomes included evaluation of adverse effect profile of the two groups. RESULTS: No significant difference was observed in the HR throughout the intraoperative period in between the two groups (P>0.05). There was statistically significant difference in SBP between the two groups starting from 1 minute after induction till 1 min after extubation (P<0.05) but not in DBP except at 1 minute after intubation (P=0.042). Significant difference in MAP was noted at 1 minute after intubation (P=0.004) and then from 5 minutes after CO2 insufflation to 1 minute after extubation (P<0.05). Incidence of adverse effects were higher in group II (P=0.02) especially incidence of hypertension requiring treatment (0.006). CONCLUSION: We conclude that under the conditions of this study, hemodynamic parameters (SBP, DBP and MAP) were better maintained in the IV as compared to the IM route that had significantly higher incidence of hypertension requiring treatment.

Current approaches to skin cancer management in organ transplant recipients.

Approximately 225,000 people are living with organ transplants in the United States. Organ transplant recipients have a greater risk of developing skin cancer, including basal cell carcinoma, squamous cell carcinoma, and malignant melanoma, with an approximately 250 times greater incidence of squamous cell carcinoma in certain transplant recipients, compared with the general population. Because skin cancers are the most common posttransplant malignancy, the resultant morbidity and mortality in these high-risk patients is quite significant.

Melanoma genetics and therapeutic approaches in the 21st century: moving from the benchside to the bedside.

Metastatic melanoma is notoriously one of the most difficult cancers to treat. Although many therapeutic regimens have been tested, very few achieve response rates greater than 25%. Given the rising incidence of melanoma and the paucity of effective treatments, there is much hope and excitement in leveraging recent genetic and molecular insights for therapeutic advantage. Over the past 30 years, elegant studies by many groups have helped decipher the complex genetic networks involved in melanoma proliferation, progression and survival, as well as several genes involved in melanocyte development and survival. Many of these oncogenic loci and pathways have become crucial targets for pharmacological development. In this article we review: (1) our current understanding of melanoma genetics within the context of signaling networks; (2) targeted therapies, including an extensive discussion of promising agents that act in the Bcl-2 signaling network; (3) future areas of research.