Publications by authors named "Arun Sharma"

773 Publications

Contribution of surgery in management of T4b head and neck cancers: A retrospective review.

Am J Otolaryngol 2022 Jul 26;43(5):103543. Epub 2022 Jul 26.

Division of Hematology and Medical Oncology, Department of Internal Medicine and Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA. Electronic address:

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http://dx.doi.org/10.1016/j.amjoto.2022.103543DOI Listing
July 2022

Identification and biotin receptor-mediated activity of a novel seleno-biotin compound that inhibits viability of and induces apoptosis in ovarian cancer cells.

Chem Biol Interact 2022 Jul 31;365:110071. Epub 2022 Jul 31.

Department of Pharmacology, Penn State Cancer Institute, CH72; Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address:

A series of seleno-biotin analogs were synthesized and their anticancer activity and mode of action were assessed using ovarian cancer cells. Compound 2, out of the other analogs, in direct comparison to biotin alone, more effectively reduced the cell viability and induced apoptosis in ovarian cancer cell lines in a dose dependent manner as demonstrated by the cell viability assay, trypan blue dye exclusion assay, Annexin V/7-AAD, and Caspase 3/7 apoptosis assays. Furthermore, compound 2 showed efficacy better than 5-fluorouracil (5-FU) and similar to cisplatin, in vitro; notably it was more cytotoxic to drug-resistant Hey A8 cells than cisplatin. The cytotoxicity of compound 2 was primarily mediated by reactive oxygen species (ROS) as demonstrated by DCFDA based ROS estimation. Biotin receptors (BR) saturation and the use of a BR negative cell line showed a significant decline in the cytotoxic ativity of the compound 2, confirming that its activity is BR-mediated. These experiments demonstrated that selenium modified biotin which contains an ester linked redox cycling selenocyanate group has the potential for human therapeutic applications against ovarian and other cancers over-expressing BR.
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http://dx.doi.org/10.1016/j.cbi.2022.110071DOI Listing
July 2022

Correction: Direct access to the optically active VAChT inhibitor vesamicol and its analogues the asymmetric aminolysis of -epoxides with secondary aliphatic amines.

Org Biomol Chem 2022 Aug 3. Epub 2022 Aug 3.

Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Correction for 'Direct access to the optically active VAChT inhibitor vesamicol and its analogues the asymmetric aminolysis of -epoxides with secondary aliphatic amines' by Arun Sharma , , 2017, , 1913-1920, https://doi.org/10.1039/C6OB02479C.
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http://dx.doi.org/10.1039/d2ob90101cDOI Listing
August 2022

Successful endovascular repair with coil embolization of ruptured right internal thoracic artery aneurysm.

J Vasc Bras 2022 11;21:e20210223. Epub 2022 Jul 11.

Post Graduate Institute of Medical Education & Research - PGIMER, Chandigarh, India.

Internal thoracic artery aneurysms (ITAAs) are rare with wide variation in clinical presentation and a high risk of rupture. Endovascular techniques are increasingly being used for treatment of such aneurysms over surgical repair in recent times. A 34-year-old male presented with progressive swelling of the right anterior chest wall for 2 weeks and was diagnosed with right internal thoracic artery aneurysm with contained rupture. He underwent successful endovascular repair with coil embolization of ruptured right ITAA. Post intervention computed tomography (CT) angiography confirmed sealing of the ruptured aneurysm with no residual filling of the sac. At six months follow-up he is doing well with complete resolution of hematoma. This case demonstrates that an endovascular approach with coil embolization is a feasible and safe option for treating the rare ruptured ITAAs.
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http://dx.doi.org/10.1590/1677-5449.20210223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296063PMC
July 2022

Congenital unilateral pulmonary vein atresia: A rare disease with successful outcome in a child.

Asian Cardiovasc Thorac Ann 2022 Jul 28:2184923221115972. Epub 2022 Jul 28.

Department of Cardiothoracic and Vascular Surgery, 29751Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Unilateral pulmonary vein atresia is a rare congenital anomaly that may occur in association with other congenital heart diseases. We report a rare case of left-sided pulmonary vein atresia in a 2-year-old child who presented with recurrent hemoptysis and was managed surgically with left pneumonectomy.
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http://dx.doi.org/10.1177/02184923221115972DOI Listing
July 2022

Evolving Experimental Platforms to Evaluate Ulcerative Colitis.

Adv Biol (Weinh) 2022 Jul 22:e2200018. Epub 2022 Jul 22.

Lurie Children's Hospital, Division of Pediatric Urology, Chicago, IL, 60611, USA.

Ulcerative colitis (UC) is a multifactorial disease defined by chronic intestinal inflammation with idiopathic origins. It has a predilection to affect the mucosal lining of the large intestines and rectum. Management of UC depends upon numerous factors that include disease pathogenesis and severity that are maintained via medical or surgical means. Chronic inflammation that is left untreated or managed poorly from a clinical stance can result in intestinal ulceration accompanied by resulting physiological dysfunction. End-stage UC is mediated by surgical intervention with the resection of diseased tissue. This can lead to numerous health-related quality of life issues but is considered a curative approach. Regimens to treat UC are ever evolving and find their basis within various platforms to evaluate and treat UC. Numerous modeling systems have been examined to delineate potential mechanisms of action. However, UC is a heterogenous disease spanning unknown genetic origins coupled with environmental factors that can influence disease outcomes and related treatment procedures. Unfortunately, there is no one-size-fits-all model to fully assess all facets of UC. Within the context of this review article, the utility of various approaches that have been employed to gain insight into different aspects of UC will be investigated.
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http://dx.doi.org/10.1002/adbi.202200018DOI Listing
July 2022

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

JAMA Otolaryngol Head Neck Surg 2022 Jul 14. Epub 2022 Jul 14.

Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease.

Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location.

Design, Setting, And Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade.

Main Outcomes And Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022.

Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (83 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries.

Conclusions And Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.
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http://dx.doi.org/10.1001/jamaoto.2022.1743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284406PMC
July 2022

Pathogenesis of Aeromonas caviae in Clariasmagur.

Microb Pathog 2022 Aug 30;169:105662. Epub 2022 Jun 30.

ICAR-Central Institute of Fisheries Education, Panch Marg, Off Yari Road, Versova, Mumbai, Maharashtra, 400061, India.

Aeromonas spp. is a pathogenic bacteria that potentially cause infection in farmed fish, including Catfishes. In the present study, dominant bacteria were isolated from diseased Clarias magur and tentatively named BLBM-05. Based on morphological, physiological, and biochemical features as well as 16S rRNA gene sequence and gyrB gene sequences (Gen Bank accession number: MT973994.1 and MZ398017.1), the bacteria in the isolate was found to be Aeromonas caviae. Further, the isolate was screened for five known virulence genes, namely β-hemolysin, lafA, exu, ompA1 and ascV. Among them, three virulence genes related to pathogenicity, including aerolysin (aer), outer membrane protein (ompA1), lateral flagella (lafA), were identified in the A. caviae isolate. The median lethal dosage (LD) of the BLBM-05 isolate for magur was determined as 1.53x10 CFU/mL. The histopathological analysis showed that the BLBM-05 isolate induced considerable histological lesions in the magur fish, including necrosis, hemolysis of erythrocytes, myolysis, hemorrhage, and desquamation in the intestinal tissue, tissue loosening, and infiltration of inflammatory cells. Drug sensitivity test showed that the isolate was susceptible to Gentamicin, Ceftazidine, Ceftrioxone, Amikacin, Tetracycline, Meropener and Oxytetracycline. The present results provide a scientific basis to identify A. caviae further, a line of treatment for magur infected by this pathogen.
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http://dx.doi.org/10.1016/j.micpath.2022.105662DOI Listing
August 2022

Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A.

iScience 2022 Jul 3;25(7):104518. Epub 2022 Jun 3.

Department of Pharmacology, Penn State University College of Medicine, Penn State Cancer Institute, Hershey, PA 17033, USA.

The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but these tumors quickly develop resistance to this treatment. We have observed increased phosphorylation of AKT1/mTOR/4EBP1 and levels of p21 in FOLFOX-resistant CRC cells. We have identified a small molecule, NSC49L, that stimulates protein phosphatase 2A (PP2A) activity, downregulates the AKT1/mTOR/4EBP1-axis, and inhibits p21 translation. We have provided evidence that NSC49L- and TRAIL-mediated sensitization is synergistically induced in p21-knockdown CRC cells, which is reversed in p21-overexpressing cells. p21 binds with procaspase 3 and prevents the activation of caspase 3. We have shown that TRAIL induces apoptosis through the activation of caspase 3 by NSC49L-mediated downregulation of p21 translation, and thereby cleavage of procaspase 3 into caspase 3. NSC49L does not affect global protein synthesis. These studies provide a mechanistic understanding of NSC49L as a PP2A agonist, and how its combination with TRAIL sensitizes FOLFOX-resistant CRC cells.
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http://dx.doi.org/10.1016/j.isci.2022.104518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218363PMC
July 2022

Morphological and functional recovery following acute and acute recurrent pancreatitis in children: A prospective sequential 2-point evaluation.

Pancreatology 2022 Jun 10. Epub 2022 Jun 10.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background: The functional and morphological recovery following an episode of acute pancreatitis (AP) in children still remains ill understood as research exploring this is limited. We aimed to characterize the morphological and functional changes in pancreas following AP and ARP (acute recurrent pancreatitis) in children.

Methods: Children with AP were followed prospectively and assessed at two time points at least 3 months apart, with the first assessment at least 3 months after the AP episode. Exocrine and endocrine functions were measured using fecal elastase and fasting blood sugar/HbA1c levels respectively. Morphological assessment was done using endoscopic ultrasound (EUS) and magnetic resonance imaging and cholangiopancreatography (MRI/MRCP).

Results: Seventy-three children (boys:59%; mean age:8.4 ± 3.2years) were studied and 21 of them (29%) progressed to ARP. Altered glucose homeostasis was seen in 19 (26%) at first and 16 (22%) at second assessment and it was significantly more in ARP group than the AP group at first (42.8%vs19.2%; p = 0.03) as well as second assessment (38.1%vs15.3%; p = 0.03). Twenty-one children (28.7%) at first and 24 (32.8%) at second assessment developed biochemical exocrine pancreatic insufficiency. EUS detected indeterminate and suggestive changes of chronic pancreatitis in 21% at first (n = 38) and 27.6% at second assessment (n = 58). On MRCP, main pancreatic duct and side branch dilatation were seen in 15 (20.5%) and 2 (2.7%) children respectively.

Conclusions: More than one-quarter of children have evidence of altered glucose homeostasis and biochemical exocrine pancreatic insufficiency following an episode of AP. Similarly, morphological features of chronicity seen in some of the children suggest that a fraction of subjects may develop chronic pancreatitis on longer follow-up.
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http://dx.doi.org/10.1016/j.pan.2022.06.008DOI Listing
June 2022

End Stage Renal Disease among Patients Undergoing Haemodialysis at a Tertiary Care Centre: A Descriptive Cross-sectional Study.

JNMA J Nepal Med Assoc 2022 May 5;60(249):448-452. Epub 2022 May 5.

Department of Internal Medicine, Shree Birendra Hospital, Chhauni, Kathmandu, Nepal.

Introduction: Chronic kidney disease is defined as structural or functional damage of the kidney persisting for three or more months. Studies have shown hypertension and diabetes as the leading causes of chronic kidney disease. The aim of this study is to find out the prevalence of end-stage renal disease patients undergoing haemodialysis in a tertiary care hospital.

Methods: This was a descriptive cross-sectional study conducted among 96 patients undergoing haemodialysis from February 13, 2021 to April 4, 2021 in the hemodialysis unit of a tertiary care centre after receiving ethical clearance from the Institutional Review Committee (Reference number: 354). Convenience sampling was done and all patients older than 18 years who were on maintenance haemodialysis on an outpatient basis were included in the study. Data were collected using a self-administered questionnaire. Data were analysed using the Statistical Package for the Social Science version 22.0. Point estimate at 95% Confidence Interval was calculated along with frequency and percentages for binary data and mean with standard deviation for continuous data.

Results: Among 96 patients undergoing haemodialysis, the prevalence of end-stage renal disease was 83 (86.45%) (79.60-93.30 at 95% Confidence Interval). The most common underlying condition was hypertensive nephropathy in 34 (40.96%) patients, followed by both hypertensive and diabetic nephropathy in 26 (31.33%) patients.

Conclusions: The prevalence of end-stage renal disease in our study was higher when compared to similar studies conducted in similar settings. Early diagnosis and adequate treatment of hypertension and diabetes could be crucial to reducing the prevalence of the end-stage renal disease.

Keywords: chronic kidney failure; chronic renal insufficiency; end stage renal disease; hemodialysis; Nepal.
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http://dx.doi.org/10.31729/jnma.7258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252224PMC
May 2022

Predictors of Professional Fulfillment and Burnout Among Otolaryngologists During the COVID-19 Pandemic.

OTO Open 2022 Apr-Jun;6(2):2473974X221100547. Epub 2022 May 17.

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Southern Illinois University, Springfield, Illinois, USA.

Objective: The goal of this study is to assess burnout and professional fulfillment during the initial weeks of the COVID-19 pandemic among otolaryngology practitioners.

Study Design: Cross-sectional survey.

Setting: International survey of otolaryngologists during a pandemic.

Methods: A cross-sectional survey was performed from April 24 to May 8, 2020, via email and social media platforms to understand the impact of the COVID-19 pandemic on otolaryngology practitioners in academic and private practice. The Professional Fulfillment Index was used to assess professional fulfillment and burnout. Burnout was divided into work exhaustion and interpersonal disengagement.

Results: Of 243 respondents, 202 completed the Professional Fulfillment Index portion of the survey. An average score ≥3 on the professional fulfillment section correlates with fulfillment, while an average score ≥1.33 on the burnout section correlates with burnout. The average score of professional fulfillment was 2.17, with 85.6% of respondents reporting lack of professional fulfillment. The average score on burnout was 1, with 40.1% of otolaryngologists reporting burnout. In multivariable analyses, females were found to have statistically lower professional fulfillment (beta = -2.28, = .010) with higher rates of work exhaustion (beta = 0.62, < .001), interpersonal disengagement (beta = 2.08, = .023), and burnout (beta = 4.49, = .002).

Conclusion: Early in the COVID-19 pandemic, most participants reported a lack of professional fulfillment while just under half experienced burnout. Female gender was associated with low professional fulfillment and high work exhaustion, interpersonal disengagement, and burnout. Attention to burnout and job satisfaction during a pandemic is critical for the appropriate well-being of otolaryngology practitioners.
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http://dx.doi.org/10.1177/2473974X221100547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118437PMC
May 2022

Analysis of the efficacy of the pectoralis major myocutaneous flap in reconstructive head and neck surgery.

Acta Otorrinolaringol Esp (Engl Ed) 2022 May-Jun;73(3):151-156

Department of Otorhinolaryngology and Head & Neck Surgery, Hamdard Institute of Medical Sciences & Research and HAHC Hospital, Jamia Hamdard University, Hamdard Nagar, Delhi, India.

Introduction: Although free flaps have been used predominantly in past decades for the soft tissue reconstruction of head and neck malignancies, Pectoralis major myocutaneous flap (PMMF) is still a reliable workhorse for patients with co-existing co-morbidities or low economic status where free flaps are not feasible.

Patients And Methods: It was a retrospective study done on 36 patients of head and neck malignancies over the period of 5 years in which PMMF was used as a method of reconstruction in our hospital. Patients were followed up for a period of one year and outcome of PMMF was evaluated.

Results: Out of 36 patients 31 were of oral cancer and 5 were of carcinoma hypopharynx. Incidence of total flap necrosis was nil and partial flap necrosis was 16.6%. Orocutaneous fistula was found in 16.6%, wound dehiscence was in 19.4% and infection was found in 13.5% of patients. Non-flap related complications were found in 13.8% of patients. 35 out of 36 patients (97.2%) eventually achieved satisfactory surgical outcome of PMMF reconstruction.

Conclusion: PMMF is a reliable method of reconstruction for head and neck malignancies especially in basic healthcare settings. With minimal expertise and groundwork, it is still a cost-effective workhorse flap for head and neck reconstruction.
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http://dx.doi.org/10.1016/j.otoeng.2020.11.006DOI Listing
May 2022

Synthesis, Electrochemical Studies, Molecular Docking, and Biological Evaluation as an Antimicrobial Agent of 5-Amino-6-cyano-3-hydroxybenzo[]coumarin Using Ni-Cu-Al-CO Hydrotalcite as a Catalyst.

ACS Omega 2022 May 26;7(18):15718-15727. Epub 2022 Apr 26.

School of Studies in Chemistry, School of Studies in Biochemistry, and Dr. APJ Abdul Kalam Central Instrumentation Facility (CIF), Jiwaji University, Gwalior, M.P. 474011, India.

New insights via a multicomponent cyclocondensation reaction of 2-hydroxy benzaldehyde acetoacetic ester and malononitrile were attained under efficient conditions. A detailed mechanistic study exhibits that the reaction via multicomponent, one-pot, two-step incooperating three-components' reactants under nominal conditions efficiently synthesizes the intermediates in shorter than reported time along with the formation of a novel compound [5-amino-6-cyano-3-hydroxybenzo[]coumarin] in the presence of Ni-Cu-Al-CO hydrotalcite as a heterogeneous catalyst. Hydrotalcite functions as an efficient and versatile catalyst as it is safe, easy to work up, and recyclable many times under ambient conditions, and the reaction time is shorter. The aforementioned conditions make these solid basic heterogeneous catalysts environmentally friendly. The product yield obtained was 89%. The product was characterized using FTIR, LCMS, and NMR. Electrochemical studies were also carried out to check the reduction and oxidation behavior. The synthesized product showed antimicrobial activity. Antimicrobial activity against human pathogens, viz, , , and , was studied by using the agar well diffusion method. The molecular docking studies of 5-amino-6-cyano-3-hydroxybenzo[]coumarin exhibit its suitable attachment at the active center of the type IIA topoisomerases and gyrase enzymes which suggest its potential antibacterial activity when compared using ciprofloxacin drug as the control.
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http://dx.doi.org/10.1021/acsomega.2c00666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096959PMC
May 2022

Role of HER2 in Prognosis of Salivary Duct Carcinoma: A Systematic Review and Meta-Analysis.

Laryngoscope 2022 May 14. Epub 2022 May 14.

Department of Otolaryngology, Head and Neck Surgery, Southern Illinois University, Springfield, Illinois, U.S.A.

Objectives: Salivary duct carcinoma (SDC) is a rare, aggressive malignancy with a poor prognosis. These tumors frequently stain positive for HER2/ErbB2, but data on the prognostic significance of HER2 status in SDC are mixed. We sought to determine whether HER2 status affects survival outcomes in SDC.

Methods: PubMed, Embase, and Web of Science databases were searched from inception to October 2020. Eligibility was restricted to studies reporting HER2/ErbB2 overexpression in histologically confirmed de novo SDC or SDC ex pleomorphic adenoma, with corresponding overall (OS) and disease-free (DFS) survival measures. Separate multivariable and univariable meta-analyses were performed using random-effects models. Statistical heterogeneity was estimated by Cochran's Q and I tests. Funnel plots were generated and Egger's test was used to assess for publication bias. The risk of bias was assessed with the Newcastle-Ottawa Scale.

Results: Of 183 unique citations, 14 studies of 663 patients were included. Most included studies determined HER2 status according to ASCO/CAP guidelines. The univariable meta-analysis did not reveal an effect between HER2 status and OS (HR 1.09, 95% CI 0.84-1.42). In the multivariable analysis, HER2 positivity was associated with a HR of 1.49 for OS (95% CI 0.96-2.30). Fewer studies reported data for DFS than OS, with no relationship between HER2 status and DFS found on multivariable or univariable meta-analyses.

Conclusion: In patients with salivary duct carcinoma, HER2 positivity was not found to be associated with worse overall survival. This information may be useful when counseling patients and considering treatment options. Laryngoscope, 2022.
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http://dx.doi.org/10.1002/lary.30214DOI Listing
May 2022

Therapeutics Targeting p53-MDM2 Interaction to Induce Cancer Cell Death.

Int J Mol Sci 2022 Apr 30;23(9). Epub 2022 Apr 30.

Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA.

Named as the guardian of the genome, p53 is a tumor suppressor that regulates cell function, often through many different mechanisms such as DNA repair, apoptosis, cell cycle arrest, senescence, metabolism, and autophagy. One of the genes that p53 activates is MDM2, which forms a negative feedback loop since MDM2 induces the degradation of p53. When p53 activity is inhibited, damaged cells do not undergo cell cycle arrest or apoptosis. As 50% of human cancers inactivate p53 by mutation, current research focuses on reactivating p53 by developing drugs that target the p53-MDM2 interaction, which includes the binding of MDM2 and phosphorylation of p53. The objective of this article is to provide a short list and description of p53-MDM2 antagonists that may be excellent candidates for inducing cancer cell death. Relevant articles were searched for and identified using online databases such as PubMed and ScienceDirect. Increasing p53 levels, by targeting the p53-MDM2 interaction, can help p53 play its role as a tumor suppressor and induce cancer cell death. Researchers have identified different compounds that can act as inhibitors, either by directly binding to MDM2 or by modifying p53 with phosphorylation. The results associated with the drugs demonstrate the importance of targeting such interactions to inhibit cancer cell growth, which indicates that the use of the compounds may improve cancer therapeutics.
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http://dx.doi.org/10.3390/ijms23095005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103871PMC
April 2022

Management of Fungal Rhinosinusitis: Experience From a Tertiary Care Centre in North India.

Cureus 2022 Apr 4;14(4):e23826. Epub 2022 Apr 4.

Department of Otorhinolaryngology & Head and Neck Surgery (ENT-HNS), Hamdard Institute of Medical Sciences and Research, Hakeem Abdul Hameed Centenary Hospital, New Delhi, IND.

Introduction Fungal rhinosinusitis (FRS) has increased over the past few decades due to the rampant use of antibiotics, steroids, immunosuppressive drugs, increased incidence of HIV and uncontrolled diabetes. The current study reviews the types, clinical presentation, microbiology, histopathology and outcomes related to FRS in a tertiary care center in North India. Methods We retrospectively reviewed the clinical and follow-up records of patients diagnosed with FRS over three years. The data reviewed included clinical workup, ophthalmological profile, comorbidities, immunological status, radiological investigations, intraoperative and histopathological findings, treatment and follow-up records. In addition, we performed a descriptive analysis of the reviewed data. Results The study consisted of 30 FRS patients (16 male, 14 female). In that, 77% of cases were of allergic FRS, while fungal ball, chronic invasive, chronic granulomatous and acute invasive FRS represented 3%, 10%, 3% and 7% cases, respectively. The most common presentation in non-invasive forms was nasal obstruction, nasal discharge, hyposmia and polyposis, while it was facial pain and headache in the invasive varieties. After appropriate medical and surgical management through endoscopic sinus surgery, the recurrence rate in non-invasive and invasive fungal sinusitis was 16.6% and 20.8%, respectively. There was nil mortality at a minimum of one year of follow-up. Conclusion The non-invasive forms of FRS are common and have a relatively mild course. Early medical and surgical intervention and management of the underlying comorbidities are the key factors in managing invasive FRS. Close follow-up after surgery is also necessary for the timely detection and management of recurrences.
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http://dx.doi.org/10.7759/cureus.23826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068350PMC
April 2022

Gastrointestinal Quality of Life in Morbidly Obese Patients Undergoing One Anastomosis Gastric Bypass (OAGB): Derivation of a "Mini GIQLI" Score.

Obes Surg 2022 07 29;32(7):2332-2340. Epub 2022 Apr 29.

Department of Surgical Disciplines All India Institute of Medical Sciences, New Delhi, India.

Background: One anastomosis gastric bypass (OAGB) is now one of the mainstream bariatric surgical procedures with proven safety and efficacy. However, data on the gastrointestinal quality of life following OAGB is lacking.

Methods: This is a retrospective analysis of a prospectively collected database, performed at a single tertiary care teaching hospital from January 2016 until March 2021. All patients undertook the Gastrointestinal Quality of Life Index (GIQLI) questionnaire. GIQLI was correlated with various parameters. Principal component analysis (PCA) was used to assess the importance of each question in the questionnaire and devise a "Mini GIQLI score".

Results: A total of 60 patients were included. The %TWL at 3 and 5 years was 26.2 ± 11.9%, 31.7 ± 11 respectively. The mean weight regain was 5.6 ± 8.5 kg. The mean GIQLI score was 125 ± 13.1. The mean scores for questions pertaining to gastrointestinal, social, psychological, and physical domains were 3.49, 3.7, 3.45, and 3.27 respectively. Scree plot of principal component analysis showed that a new score ("Mini GIQLI") combining only 5 questions had good correlation with the overall GIQOL score (r = 0.842). The five questions related to anxiety, fatigue, feeling unwell, loss of endurance, and feeling unfit.

Conclusions: Patients report a good score on GIQLI assessment following OAGB. The Mini GIQLI score is a quicker tool with good correlation to the full-length GIQLI score.
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http://dx.doi.org/10.1007/s11695-022-06080-2DOI Listing
July 2022

Influence of ceramide on lipid domain stability studied with small-angle neutron scattering: The role of acyl chain length and unsaturation.

Chem Phys Lipids 2022 07 26;245:105205. Epub 2022 Apr 26.

Department of Chemistry, University of Tennessee, Knoxville 37996, TN, USA. Electronic address:

Ceramides and diacylglycerols are groups of lipids capable of nucleating and stabilizing ordered lipid domains, structures that have been implicated in a range of biological processes. Previous studies have used fluorescence reporter molecules to explore the influence of ceramide acyl chain structure on sphingolipid-rich ordered phases. Here, we use small-angle neutron scattering (SANS) to examine the ability of ceramides and diacylglycerols to promote lipid domain formation in the well-characterized domain-forming mixture DPPC/DOPC/cholesterol. SANS is a powerful, probe-free technique for interrogating membrane heterogeneity, as it is differentially sensitive to hydrogen's stable isotopes protium and deuterium. Specifically, neutron contrast is generated through selective deuteration of lipid species, thus enabling the detection of nanoscopic domains enriched in deuterated saturated lipids dispersed in a matrix of protiated unsaturated lipids. Using large unilamellar vesicles, we found that upon replacing 10 mol% DPPC with either C16:0 or C18:0 ceramide, or 16:0 diacylglycerol (dag), lipid domains persisted to higher temperatures. However, when DPPC was replaced with short chain (C6:0 or C12:0) or very long chain (C24:0) ceramides, or ceramides with unsaturated acyl chains of any length (C6:1(3), C6:1(5), C18:1, and C24:1), as well as C18:1-dag, lipid domains were destabilized, melting at lower temperatures than those in the DPPC/DOPC/cholesterol system. These results show how ceramide acyl chain length and unsaturation influence lipid domains and have implications for how cell membranes might modify their function through the generation of different ceramide species.
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http://dx.doi.org/10.1016/j.chemphyslip.2022.105205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320172PMC
July 2022

SERUM PROCALCITONIN AS A PROGNOSTIC MARKER IN ACUTE SEVERE ULCERATIVE COLITIS: A PROSPECTIVE STUDY.

Arq Gastroenterol 2022 Jan-Mar;59(1):75-79

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Procalcitonin may be increased in active ulcerative colitis (UC). We investigated the role of procalcitonin in predicting response in acute severe UC (ASUC).

Methods: Consecutive patients with ASUC diagnosed on basis of Truelove and Witts criteria were enrolled. Serum procalcitonin levels for consecutive patients were measured at admission and day 3. We assessed role of procalcitonin values at presentation and at day 3 in assessing response on day 3 (Oxford's criteria) and need for second line therapy (day 28).

Results: Of fifty patients (23 males, mean age: 35.98±13.8 years), 16 did not respond (day 3). Ten (20%) patients required second-line therapy. Baseline procalcitonin was significantly associated with response on day 3 (P=0.016). There was no association between day 1 or day 3 procalcitonin and need for second-line rescue therapy.

Conclusion: Serial procalcitonin is not an effective biomarker for predicting outcomes or need for second line therapy in ASUC.
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http://dx.doi.org/10.1590/S0004-2803.202200001-14DOI Listing
April 2022

Fighting Carcinogenesis with Plant Metabolites by Weakening Proliferative Signaling and Disabling Replicative Immortality Networks of Rapidly Dividing and Invading Cancerous Cells.

Curr Drug Deliv 2022 Apr 14. Epub 2022 Apr 14.

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.

Background: Cancer, an uncontrolled multistage process causing swift division of cells, is a leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors, resisting cell death, and replicative immortality drive the tumor progression by resisting therapeutic action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling, enabling replicative immortality through telomere dysfunction.

Area Covered: The conventional genotoxic drugs have several off-target and collateral side effects associated with them. Thus, the need for the therapies targeting cyclin-dependent kinases or P13K signaling pathway to expose cancer cells to immune destruction, deactivation of invasion and metastasis, and maintaining cellular energetics is imperative. Compounds with anticancer attributes isolated from plant and rich in alkaloids, terpenes, and polyphenols have proven to be less toxic and highly target-specific, making them biologically significant. This has opened a gateway for the exploration of more novel plant molecules by signifying their role as anticancer agents in synergy and alone making them effective than the existing cytotoxic regimens.

Expert Opinion: In this context, the current review presented recent data on cancer cases around the globe along with discussing the fundamentals of proliferative signaling and replicative immortality of cancer cells. Recent findings were also highlighted including antiproliferative and antireplicative action of plant-derived compounds besides explaning the need for improving drug delivery systems.
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http://dx.doi.org/10.2174/1567201819666220414085606DOI Listing
April 2022

Congenitally corrected transposition with absent pulmonary valve: Hitherto unreported association.

J Card Surg 2022 Jul 12;37(7):2100-2102. Epub 2022 Apr 12.

Department of Radiodiagnosis, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Absent pulmonary valve has usually been described in association with tetralogy of Fallot. Present case highlights its association with congenitally corrected transposition which has not been reported so far in literature.
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http://dx.doi.org/10.1111/jocs.16502DOI Listing
July 2022

Emotional distress among survivors of adolescent and young adult cancer or adult cancer.

Ann Epidemiol 2022 08 9;72:48-56. Epub 2022 Apr 9.

Department of Head and Neck Surgery and Communication Sciences, Duke University School of Medicine, Durham, NC; Department of Population Health Sciences, Duke University School of Medicine, Durham, NC.

Purpose: We examined emotional distress in cancer survivors diagnosed as adolescents or young adults (AYAs) versus cancer survivors diagnosed as middle/older adults and versus the general population without a history of cancer.

Methods: Using the 2014-2017 National Health Interview Surveys, 2500 AYA survivors (initial cancer diagnosed between aged 15-39 years) were matched with 2500 middle/older adult survivors (initial cancer diagnosed at aged ≥40 years) as well as with 1609 from the general population without a history of cancer. Multinomial logistic regression models estimated the risk of emotional distress (measured using the validated Kessler distress (K6) scale) in the study population (AYA vs. middle/older adult cancer survivors and vs. general population without cancer), adjusting for known covariates.

Results: Emotional distress was more prevalent among AYAs (average age 52.8 ± 19.1 years) than middle/older adult (average age 67.4 ± 14.0 years) cancer survivors (moderate: 25.5% vs. 19.4%; and severe: 6.4% vs. 4.4% [P < .0001]); however, there was no difference in emotional distress between AYA cancer survivors (moderate: 26.8% and severe: 7.5%) versus general population without cancer (moderate: 23.7% and severe: 6.2%). In the multivariable multinomial analyses, AYA cancer survivors had higher risk of reporting emotional distress (adjusted relative risk = 1.45; 95% confidence interval = 1.13-1.86) than middle/older adult cancer survivors.

Conclusion: Psychosocial support may be especially needed for cancer survivors diagnosed as adolescents or young adults to mitigate adverse psychosocial outcomes.
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http://dx.doi.org/10.1016/j.annepidem.2022.03.014DOI Listing
August 2022

Marijuana use among US adults with cancer: findings from the 2018-2019 Behavioral Risk Factor Surveillance System.

J Cancer Surviv 2022 Apr 9. Epub 2022 Apr 9.

Simons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, USA.

Purpose: This study aimed to assess the prevalence of current marijuana use and to identify the factors associated with its use among US adults with cancer living in 17 US states and territories.

Methods: Data from the 2018-2019 Behavioral Risk Factor Surveillance System Marijuana Use module were analyzed. The analytic sample included 13,174 adults with cancer. The primary outcome was current marijuana use. Weighted, multivariable logistic regression was used to identify sociodemographic, health, and healthcare factors associated with marijuana use.

Results: Overall, 9.2% of adult cancer survivors (n = 13,174; weighted 5.7 million) reported marijuana current use, 51.3% of whom used it for medical reasons only, with 65.2% reporting smoking as the main method of administration. Adult cancer survivors were significantly more likely to use marijuana if they were younger (odds ratio [OR] for 55-64 years old, 0.60; 95% CI, 0.38-0.93, vs. 18-44); male (OR for female, 0.65; 95% CI, 0.48-0.87, vs. male); non-Hispanic black (OR, 2.00; 95% CI, 1.21-3.33; P < 0.01, vs. non-Hispanic white); living with depression (OR, 1.58; 95% CI, 1.17-2.14); and current (OR, 3.23; 95% CI, 2.20-4.74) or former tobacco smoker (OR, 2.40; 95% CI, 1.70-3.38, vs. never smoker) and binge drinker (OR, 2.25; 95% CI, 1.53-3.29, vs. non-binge drinker).

Conclusions: Among a large cohort of US adults with cancer, marijuana use was commonly reported, and certain subgroups were at increased likelihood of marijuana use.

Implications For Cancer Survivors: Health professionals should identify the risk factors for marijuana use, especially as more states legalize medical and recreational marijuana use.
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http://dx.doi.org/10.1007/s11764-021-01138-zDOI Listing
April 2022

Ortner's Syndrome Due to Giant Thoracic Aortic Aneurysm.

J Invasive Cardiol 2022 04;34(4):E346

Department of Cardiology, Advanced Cardiac Center, PGIMER Chandigarh 160012 India.

Ortner's syndrome is hoarseness of the voice caused by enlarged cardiac structures compressing the left recurrent laryngeal nerve (LRLN). The LRLN is vulnerable for impingement by cardiac structures due to its anatomical course. LRLN is longer and it hooks below the arch of the aorta, posterior to the ligamentum arteriosum before ascending toward the tracheo- esophageal groove. Ortner's syndrome has been commonly described with left atrial enlargement due to mitral stenosis; however, other causes like aortic aneurysm, pulmonary artery aneurysm, and aortic dissection have been described. Although rare, hoarseness of the voice could be the only presenting complaint in aortic aneurysms as in the case described herein.
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April 2022

A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases.

Eur J Pharmacol 2022 May 23;923:174910. Epub 2022 Mar 23.

Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Pharmacology and Toxicology Department, College of Pharmacy, Ain Shams University, Cairo, Egypt.

Liver fibrosis is a common chronic hepatic disease. This study was done to examine the effect of pyridoxamine against thioacetamide-induced hepatic fibrosis. Animals were divided into four groups (1) control group; (2) Thioacetamide group (200 mg/kg, i.p.) twice a week for eight weeks; (3) Pyridoxamine-treated group treated with pyridoxamine (100 mg/kg/day, i.p.) for eight weeks; (4) Thioacetamide and pyridoxamine group, in which pyridoxamine was given (100 mg/kg/day, i.p.) during thioacetamide injections. Thioacetamide treatment resulted in hepatic dysfunction manifested by increased serum levels of bilirubin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Oxidative stress was noted by increased hepatic lipid peroxidation and decreased glutathione (GSH). Increased concentrations of total nitrite/nitrate, advanced glycation end products (AGEs), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), matrix metalloproteinases (MMP-2&9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were noticed in hepatic tissues. Immunostaining sections also revealed overexpression of MMP-2, MMP-9 and collagen IV. Liver fibrosis was confirmed by severe histopathological changes. Pyridoxamine improved the assessed parameters. Moreover, histopathological and immunohistological studies supported the ability of pyridoxamine to reduce liver fibrosis. The findings of the present study provide evidence that pyridoxamine is a novel target for the treatment of liver fibrosis.
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http://dx.doi.org/10.1016/j.ejphar.2022.174910DOI Listing
May 2022

Hyperleptinaemia and its Association with Postprandial Hypertriglyceridemia and Glucose Intolerance.

Indian J Endocrinol Metab 2021 Sep-Oct;25(5):443-449. Epub 2022 Jan 12.

Department of Central Animal House Facility, University College of Medical Sciences (University of Delhi) and GTB Hospital, Delhi, India.

Introduction: Leptin resistance is believed to cause insulin resistance though the exact mechanism is not fully understood. The present study aims to investigate the temporal profile of postprandial triglyceride (PPTG) and leptin levels, and their association with each other as well as with markers of metabolic syndrome.

Materials And Methods: Serum leptin and PPTG levels were measured longitudinally till 26 weeks in Wistar rats fed on controlled diet (group 1) and high sucrose diet (HSD) (group 2). Two additional groups fed on HSD were taken and treated with pioglitazone (group 3) and atorvastatin (group 4). Body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose intolerance were also measured during this period. Comparison of the groups were done and Pearson's correlation coefficient was used to ascertain the association.

Results: Leptin levels were significantly higher in all three groups receiving HSD compared to controlled diet group from week 2 to week 26 ( < 0.01). The postprandial triglyceride area under the curve (PPTG AUCs) were significantly higher in group 2 than controls during this period ( < 0.001). Body weight, HOMA-IR and glucose AUC were found to be significantly higher in group 2 rats than controls only from week 6, 8, and 12 respectively. In HSD-fed rats, but not in control, mean serum leptin levels from 2-26 weeks as well as peak (10 week) and 26 week were strongly associated with corresponding as well as preceding PPTG levels. Leptin levels significantly predicted HOMA-IR and prediabetes in group 2.

Conclusion: This study found significant hyperleptinemia associated with postprandial hypertriglyceridemia that predicted insulin resistance and prediabetes in high sucrose diet-fed rats.
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http://dx.doi.org/10.4103/ijem.ijem_393_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923330PMC
January 2022

Nanoemulsions (O/W) containing essential oil: development, characterization, stability study, and evaluation of in vitro anti-bacterial, anti-inflammatory, anti-diabetic activities.

Bionanoscience 2022 2;12(2):540-554. Epub 2022 Mar 2.

PG Dept. of Biotechnology, Lyallpur Khalsa College, Jalandhar, Punjab India.

Essential oil from is immensely useful in various sectors like food, pharmaceutical, and cosmetic industries. Since this oil is hydrophobic, unstable, and volatile, hence encapsulation by using nanoemulsions technology is the best way to protect it. This study reports biosynthesis of O/W (oil/water) nanoemulsions based on essential oil from and analysis of its biological activities. O/W nanoemulsions were prepared by using tween 20/80, sodium dodecyl sulphate as surfactants, and ethanol as co-surfactants. Fingerprinting of nanoemulsions using UV, fluorescent, and FT-IR was studied along with other parameters like pH and conductivity. Biological activities like antibacterial, anti-inflammatory, and anti-diabetic activities and drug release pharmokinetics were evaluated. Ethanol containing nanoemulsions was noticeably smaller than other nanoemulsions. Encapsulation efficiency of nanoemulsions was in the range from 41 to 60%. Nanoemulsions were spherical in shape and stable even after 50 days of storage. Appreciable biological activities like anti-bacterial, anti-inflammatory, and anti-diabetic activities were detected. Drug kinetic study revealed that nanoemulsions exhibited Korsmeyer-Peppas model. Based on this, the possible role of lemon grass oil-based nanoemulsions in cosmetic, food, and pharma sectors has been discussed.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12668-022-00964-4.
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http://dx.doi.org/10.1007/s12668-022-00964-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889062PMC
March 2022

In situ generation of a Zwitterionic fluorescent probe for detection of human serum albumin protein.

Anal Biochem 2022 06 4;646:114630. Epub 2022 Mar 4.

Department of Physical Sciences, Arkansas Tech University, Russellville, AR, 72801, United States.

In this article, a new approach for human serum albumin selective fluorophore design has been reported. The fluorophore reported here comprises a substituted phenol donor and a cationic benzo[e]indolium acceptor connected with a π bond. Originally, the cationic fluorophore did not bind with human serum albumin. Upon deprotonation of the phenolic-OH by a water molecule the cationic form was transformed into an active zwitterionic form. Spectroscopic studies and theoretical calculations revealed that the new active form remained in a zwitterionic state in neutral aqueous solution, and it formed a strong supramolecular complex with human serum albumin. The spontaneous complexation resulted multi-fold increase of fluorescence intensity which increased linearly with the concentrations of the protein, thus giving an analytical tool to monitor human serum albumin in aqueous samples. We believe, this simple strategy applied on appropriate fluorogenic scaffolds would prove useful to develop new and improved turn-on fluorescent probes for pH regulated biological applications.
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http://dx.doi.org/10.1016/j.ab.2022.114630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018593PMC
June 2022
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