Publications by authors named "Harsimran Kaur"

130 Publications

CT Findings of COVID-19-associated Pulmonary Mucormycosis: A Case Series and Literature Review.

Radiology 2021 Aug 31:211583. Epub 2021 Aug 31.

Department of Pulmonary Medicine, PGIMER, Chandigarh, India.

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http://dx.doi.org/10.1148/radiol.2021211583DOI Listing
August 2021

Multiple Fusarium brain abscesses in a young child.

Childs Nerv Syst 2021 Aug 10. Epub 2021 Aug 10.

Department of Pediatrics, Division of Pediatric Critical Care, Advanced Pediatrics Centre, PGIMER, Madhya Marg, Sector 12, Chandigarh, 160012, India.

Isolated intracranial fungal infection is infrequent and mostly seen in high-risk, immunocompromised patients. Fusarium, a primary plant fungus, rarely contributes to such disease. Amongst the very few cases of Fusarium brain abscess that have been reported, the infection has occurred mostly in adults. We present a case of a 6-year-old boy with tuberculous meningitis diagnosed with multiple Fusarium brain abscess caused by Fusarium falciforme during his clinical course. An immunocompromised state secondary to tuberculous meningitis presumably led to this infection. After tapping the abscesses, the child was treated with a combination of amphotericin B, voriconazole and terbinafine. Despite an aggressive therapy, he remained in poor neurological state. This is the second report of an isolated Fusarium abscess in pediatric age and the first one in a young child and provides pertinent review of this unusual central nervous system fungal infection. Such unusual infectious spectrum should be borne in mind in patients with co-existent immunosuppression.
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http://dx.doi.org/10.1007/s00381-021-05320-7DOI Listing
August 2021

Advanced nanomedicine approaches applied for treatment of skin carcinoma.

J Control Release 2021 Sep 6;337:589-611. Epub 2021 Aug 6.

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. Electronic address:

Skin-cancer is the commonest malignancy affecting huge proportion of the population, reaching heights in terms of morbidity. The treatment strategies are presently focusing on surgery, radiation and chemotherapy, which eventually cause destruction to unaffected cells. To overcome this limitation, wide range of nanoscaled materials have been recognized as potential carriers for delivering selective response to cancerous cells and neoplasms. Nanotechnological approach has been tremendously exploited in several areas, owing to their functional nanometric dimensions. The alarming incidence of skin cancer engenders burdensome effects worldwide, which is further awakening innovational medicinal approaches, accompanying target specific drug delivery tools for coveted benefits to provide reduced toxicity and tackle proliferative episodes of skin cancer. The developed nanosystems for anti-cancer agents include liposomes, ethosomes, nanofibers, solid lipid nanoparticles and metallic nanoparticles, which exhibit pronounced outcomes for skin carcinoma. In this review, skin cancer with its sub-types is explained in nutshell, followed by compendium of specific nanotechnological tools presented, in addition to therapeutic applications of drug-loaded nano systems for skin cancer.
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http://dx.doi.org/10.1016/j.jconrel.2021.08.003DOI Listing
September 2021

A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells.

NAR Cancer 2021 Sep 9;3(3):zcab027. Epub 2021 Jul 9.

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.

Resistance to anti-estrogen therapy is an unsolved clinical challenge in successfully treating ER+ breast cancer patients. Recent studies have demonstrated the role of non-genetic (i.e. phenotypic) adaptations in tolerating drug treatments; however, the mechanisms and dynamics of such non-genetic adaptation remain elusive. Here, we investigate coupled dynamics of epithelial-mesenchymal transition (EMT) in breast cancer cells and emergence of reversible drug resistance. Our mechanism-based model for underlying regulatory network reveals that these two axes can drive one another, thus enabling non-genetic heterogeneity in a cell population by allowing for six co-existing phenotypes: epithelial-sensitive, mesenchymal-resistant, hybrid E/M-sensitive, hybrid E/M-resistant, mesenchymal-sensitive and epithelial-resistant, with the first two ones being most dominant. Next, in a population dynamics framework, we exemplify the implications of phenotypic plasticity (both drug-induced and intrinsic stochastic switching) and/or non-genetic heterogeneity in promoting population survival in a mixture of sensitive and resistant cells, even in the absence of any cell-cell cooperation. Finally, we propose the potential therapeutic use of mesenchymal-epithelial transition inducers besides canonical anti-estrogen therapy to limit the emergence of reversible drug resistance. Our results offer mechanistic insights into empirical observations on EMT and drug resistance and illustrate how such dynamical insights can be exploited for better therapeutic designs.
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http://dx.doi.org/10.1093/narcan/zcab027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271219PMC
September 2021

Efficacy and tolerability of Melatonin vs Triclofos to achieve sleep for pediatric electroencephalography: A single blinded randomized controlled trial.

Eur J Paediatr Neurol 2021 Jul 7;34:14-20. Epub 2021 Jul 7.

Department of Pediatrics, Bharati Vidyapeeth Deemed University Medical College, Pune, India. Electronic address:

Purpose: To compare Melatonin with Triclofos for efficacy (proportion of successful EEG, need of augmentation, sleep onset latency (SOL), yield of discharges, duration of sleep, presence and grade of artifacts) and tolerability (adverse effect profile).

Methods: A randomized trial was performed (block randomization). All children were advised regarding sleep deprivation, EEG technician administered the drug. EEG was labelled successful if at least 30 min of record could be obtained (sleep with or without awake state). Pediatric neurologist reported the EEG findings-sleep onset latency, epileptiform abnormalities and graded the artifacts (excess beta activity and movement artifacts if present). The parents were interviewed telephonically next day by a pediatric resident for any adverse effects. The parents, pediatric neurologist and pediatric resident were blinded for the drug given.

Results: 228 children were randomized (114 each received Melatonin and Triclofos). Both the groups were comparable at baseline for age group and demographic data. The proportion of successful EEG was 89.4% in Melatonin and 91.2% in Triclofos. First dose was effective in 64% in Melatonin and 63.15% in Triclofos group. Augmentation dose was needed in 25.4% in Melatonin and 28% in Triclofos group. Mean total sleep duration was 80 min after Melatonin and 82.39 after Triclofos administration. Adverse effects were observed in 6.14% of Melatonin and 8.65% of Triclofos group. None of the results were statistically significant.

Conclusion: There was no significant difference between efficacy and tolerability of Melatonin and Triclofos. Melatonin can be safely used to achieve sleep for EEG in children.
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http://dx.doi.org/10.1016/j.ejpn.2021.06.006DOI Listing
July 2021

Clinical Spectrum, Molecular Characterization, Antifungal Susceptibility Testing of spp. From India and Description of a Novel Species sp. nov.

Front Cell Infect Microbiol 2021 2;11:686120. Epub 2021 Jul 2.

Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Introduction: spp. are important opportunist pathogens causing subcutaneous or even fatal disseminated infections in otherwise both immunosuppressed and healthy individuals but there are no systematic studies on the isolates of species from India.

Methods: Twenty-four isolates of species were retrieved from the National Culture Collection of Pathogenic Fungi (NCCPF) and identified phenotypically and by molecular methods (ITS region sequencing) followed by antifungal susceptibility testing (AFST) as per CLSI-M38A3 guidelines. A review of the literature of cases from India was performed up to 1 January 2021 using the Medline and Cochrane database.

Results: (n = 8), (n = 6),  (n = 6),  (n = 1), (n = 1), (n = 1) were identified and the sequencing of and revealed a novel species, sp. nov. (n = 1). The ITS sequence phylogram of revealed that the majority (83%) formed a separate cluster close to type A while majority (75%) of were type B. The MIC50 (mg/L) of amphotericin, itraconazole, voriconazole, micafungin, caspofungin, anidulafungin, and posaconazole, was 1, 0.25, 0.125, 0.12, 0.125, 0.062, and 0.062, respectively. Sixteen more cases were identified on the literature review and a significant association of with history of surgical procedures (p = 0.013), invasive disease (p = 0.032) and of with tuberculosis (p = 0.026) was seen.

Conclusion: This, to the best of our knowledge is the first study from India elucidating the molecular and clinical characteristics of species and the first Indian report of human infection due to and
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http://dx.doi.org/10.3389/fcimb.2021.686120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284318PMC
July 2021

The Significance of the Mediterranean Diet in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review.

Cureus 2021 Jun 13;13(6):e15618. Epub 2021 Jun 13.

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Non-alcoholic fatty liver disease (NAFLD) is the accumulation of intrahepatic fat occurring in the absence of alcohol abuse. The fatty changes in the liver are often the beginning of sequelae of complications, potentially causing steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. The Mediterranean diet is not only a way of eating but is considered a lifestyle and primarily consists of a plant-based diet, with olive oil as the primary lipid. In this study, we reviewed the effectiveness of the Mediterranean diet on NAFLD and its efficacy in disease management. This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2009 guidelines. The PubMed database was used to gather articles, using the following terms individually and in combination, "Mediterranean diet," "non-alcoholic fatty liver disease," "insulin resistance," "metabolic syndrome," "omega-3-fatty acids." A quality appraisal was completed to include 14 articles in this systematic review. The studies discuss the correlation between the Mediterranean diet and its role in preventing and treating NAFLD. Olive oil is the major monounsaturated fatty acid, whereas nuts, seeds, and fish consist largely of polyunsaturated fatty acids, both of which are essential components of the Mediterranean diet. The plant-based diet, having sufficient amounts of vegetables, legumes, and fruits, provides its anti-oxidant and anti-inflammatory effects, playing a fundamental role in preventing oxidative stress damage. Olive oil polyphenols increase apoptosis and cell cycle arrest. They also decrease proliferation and angiogenesis, all of which prevent neoplasia. Adapting the Mediterranean lifestyle has shown promising effects in NAFLD, reducing overall mortality and morbidity.
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http://dx.doi.org/10.7759/cureus.15618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275052PMC
June 2021

Rhizopus homothallicus: An emerging pathogen in era of COVID-19 associated mucormycosis.

Indian J Med Microbiol 2021 Jul 12. Epub 2021 Jul 12.

Department of Medical Microbiology PGIMER, Chandigarh, India.

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http://dx.doi.org/10.1016/j.ijmmb.2021.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275028PMC
July 2021

Designing aromatic N-cadherin mimetic short-peptide-based bioactive scaffolds for controlling cellular behaviour.

J Mater Chem B 2021 Aug 15;9(29):5898-5913. Epub 2021 Jul 15.

Institute of Nano Science and Technology, Sector-81, Knowledge City, Sahibzada Ajit Singh Nagar, Punjab, Pin-140306, India.

The development of suitable biomaterials is one of the key factors responsible for the success of the tissue-engineering field. Recently, significant effort has been devoted to the design of biomimetic materials that can elicit specific cellular responses and direct new tissue formation mediated by bioactive peptides. The success of the design principle of such biomimetic scaffolds is mainly related to the cell-extracellular matrix (ECM) interactions, whereas cell-cell interactions also play a vital role in cell survival, neurite outgrowth, attachment, migration, differentiation, and proliferation. Hence, an ideal strategy to improve cell-cell interactions would rely on the judicious incorporation of a bioactive motif in the designer scaffold. In this way, we explored for the first time the primary functional pentapeptide sequence of the N-cadherin protein, HAVDI, which is known to be involved in cell-cell interactions. We have formulated the shortest N-cadherin mimetic peptide sequence utilizing a minimalistic approach. Furthermore, we employed a classical molecular self-assembly strategy through rational modification of the basic pentapeptide motif of N-cadherin, i.e. HAVDI, using Fmoc and Nap aromatic moieties to modify the N-terminal end. The designed N-cadherin mimetic peptides, Fmoc-HAVDI and Nap-HAVDI, self-assembled to form a nanofibrous network resulting in a bioactive peptide hydrogel at physiological pH. The nanofibrous network of the pentapeptide hydrogels resembles the topology of the natural ECM. Furthermore, the mechanical strength of the gels also matches that of the native ECM of neural cells. Interestingly, both the N-cadherin mimetic peptide hydrogels supported cell adhesion and proliferation of the neural and non-neural cell lines, highlighting the diversity of these peptidic scaffolds. Further, the cultured neural and non-neural cells on the bioactive scaffolds showed normal expression of β-III tubulin and actin, respectively. The cellular response was compromised in control peptides, which further establishes the significance of the bioactive motifs towards controlling the cellular behaviour. Our study indicated that our designer N-cadherin-based peptidic hydrogels mimic the structural as well as the physical properties of the native ECM, which has been further reflected in the functional attributes offered by these scaffolds, and thus offer a suitable bioactive domain for further use as a next-generation material in tissue-engineering applications.
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http://dx.doi.org/10.1039/d1tb00598gDOI Listing
August 2021

Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology.

Cureus 2021 Jun 3;13(6):e15433. Epub 2021 Jun 3.

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Hematological malignancies often develop due to a vast spectrum of environmental and genetic etiologies. Chronic neutrophilic leukemia (CNL) can be described as a (Philadelphia chromosome)-negative myeloproliferative neoplastic disease with various genetic mutations that may directly or indirectly play a role in its pathogenesis. A well-established mutation in CNL is the (a cytokine receptor) which has been incorporated into the diagnostic criteria for the disease. However, evidence of other mutations such as , , and has also shed more light on the pathogenesis of this condition. Due to the unknown incidence and heterogeneous presentation of the disease, the diagnosis and management are often difficult and lack satisfactory data. The purpose of this review is to yield further insight into a disease that lacks awareness in the medical community. Using PubMed as a database, relevant studies and case reports were reviewed. The data compiled were used to acknowledge the disease in terms of etiology, clinical manifestation, molecular pathogenesis, and available treatment modalities. Though existing treatment modalities have been shown to induce clinical improvement, the outcomes are not reliable, and further research is required to reach a comprehensive "standard of care" for the disease.
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http://dx.doi.org/10.7759/cureus.15433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253489PMC
June 2021

False-positive HIV serology, Candida lusitaniae pneumonia, and a novel mutation in the CYBB gene.

Immunobiology 2021 Jul 2;226(4):152110. Epub 2021 Jul 2.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Electronic address:

Background: Chronic granulomatous disease (CGD) presents with a myriad of clinical manifestations pertaining to both immunodeficiency and hyperinflammation. Although Candida infection is a signature organism for patients with CGD, C. lusitaniae pneumonia in CGD has rarely been reported. C. lusitaniae is a ubiquitous ascomycete predominantly infecting immunocompromised hosts and has the potential to rapidly develop multi-drug resistance during therapy. Additionally, C. lusitaniae is recognized for its variable resistance against amphotericin B. To date, C. lusitaniae infections in patients with CGD have not been reviewed in detail. False-positive HIV serology, resulting from polyclonal hypergammaglobulinemia, has been reported in association with several infections, auto-immune diseases, and malignancies. Although CGD is often associated with hypergammaglobulinemia, a false-positive HIV serology in CGD has not been reported previously.

Procedure: We report a combination of unique findings in a child with CGD - a false-positive HIV serology, Candida lusitaniae pneumonia, and a novel CYBB mutation. We also provide a detailed review of C. lusitaniae infections in patients with CGD.

Results: In patients with CGD, C. lusitaniae has been reported to cause lymphadenitis (cervical, abdominal), fungemia, meningoencephalitis, or abscesses in the liver and spleen. Many CGD patients with C. lusitaniae infection have associated inflammatory complications of the gut (inflammatory bowel disease, colitis). Additionally, almost all C. lusitaniae infections in CGD have been reported in young infants or in patients receiving long-term immunosuppressive therapy. This reflects that further immunocompromise (in addition to the underlying immune deficiency in CGD) may specifically predispose to C. lusitaniae infection (unlike other candidal infections). Most of the CGD patients with documented C. lusitaniae infection have X-linked form of the disease which generally has been postulated to have a more severe clinical phenotype than the autosomal recessive forms of the disease.

Conclusions: HIV serology may be positive in patients with CGD and other inborn errors of immunity as a result of hypergammaglobulinemia. C. lusitaniae, which may have peculiar and evolving antimicrobial sensitivity patterns, needs to be considered in patients with CGD and pneumonia. Lastly, to reiterate, CGD should to be considered in patients with proven C. lusitaniae infection.
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http://dx.doi.org/10.1016/j.imbio.2021.152110DOI Listing
July 2021

Current Insight into the Therapeutic Potential of Phytocompounds and their Nanoparticle-based Systems for Effective Management of Lung Cancer.

Anticancer Agents Med Chem 2021 Jul 8. Epub 2021 Jul 8.

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi -110062, India.

Lung cancer is the second most common cancer and the primary cause of cancer-related death in both men and women worldwide. Due to diagnosis at an advanced stage, it is associated with high mortality in the majority of patients. At present, various treatment approaches are available such as chemotherapy, surgery, and radiotherapy. However, all these approaches usually cause serious side effects like degeneration of normal cells, bone marrow depression, alopecia, extensive vomiting, etc. To overcome the aforementioned problems, researchers have focused on the alternative therapeutic approach in which various natural compounds are reported, which possessed anti-lung cancer activity. Phytocompounds exhibit their anti-lung cancer activity via targeting various cell-signaling pathways, apoptosis, cell cycle arrest, and regulating antioxidant status and detoxification. Apart from the excellent anti-cancer activity, clinical administration of phytocompounds is confined because of their high lipophilicity and low bioavailability. Therefore, researchers show their concern in the development of a stable, safe, and effective approach of treatment with minimal side effects by the development of nanoparticle-based delivery of these phytocompounds to the target site. Targeted delivery of phytocompound through nanoparticles overcomes the aforementioned problems. In this article, the molecular mechanism of phytocompounds, their emerging combination therapy, and their nanoparticles-based delivery systems in the treatment of lung cancer have been discussed.
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http://dx.doi.org/10.2174/1871520621666210708123750DOI Listing
July 2021

Enthralling the impact of engineered nanoparticles on soil microbiome: A concentric approach towards environmental risks and cogitation.

Ecotoxicol Environ Saf 2021 Oct 30;222:112459. Epub 2021 Jun 30.

Botany and Microbiology Department, King Saud University, Riyadh, Saudi Arabia. Electronic address:

Nanotechnology is an avant-garde field of scientific research that revolutionizes technological advancements in the present world. It is a cutting-edge scientific approach that has undoubtedly a plethora of functions in controlling environmental pollutants for the welfare of the ecosystem. However, their unprecedented utilization and hysterical release led to a huge threat to the soil microbiome. Nanoparticles(NPs) hamper physicochemical properties of soil along with microbial metabolic activities within rhizospheric soils.Here in this review shed light on concentric aspects of NP-biosynthesis, types, toxicity mechanisms, accumulation within the ecosystem. However, the accrual of tiny NPs into the soil system has dramatically influenced rhizospheric activities in terms of soil properties and biogeochemical cycles. We have focussed on mechanistic pathways engrossed by microbes to deal with NPs.Also, we have elaborated the fate and behavior of NPs within soils. Besides, a piece of very scarce information on NPs-toxicity towards environment and rhizosphere communities is available. Therefore, the present review highlights ecological perspectives of nanotechnology and solutions to such implications. We have comprehend certain strategies such as avant-garde engineering methods, sustainable procedures for NP synthesis along with vatious regulatory actions to manage NP within environment. Moreover, we have devised risk management sustainable and novel strategies to utilize it in a rationalized and integrated manner. With this background, we can develop a comprehensive plan about NPs with novel insights to understand the resistance and toxicity mechanisms of NPs towards microbes. Henceforth, the orientation towards these issues would enhance the understanding of researchers for proper recommendation and promotion of nanotechnology in an optimized and sustainable manner.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112459DOI Listing
October 2021

Distinct role of HAMP and HAMP-like linker domains in regulating the activity of Hik1p, a hybrid histidine kinase 3 from Magnaporthe oryzae.

Mol Genet Genomics 2021 Sep 1;296(5):1135-1145. Epub 2021 Jul 1.

CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh, India.

Nik1 orthologs or group III hybrid histidine kinases (HHK3) represent a unique cytoplasmic osmosensor that act upstream of HOG/p38 MAPK pathway in fungi. It is an important molecular target for developing new antifungal agents against human pathogens. HHK3 orthologs contain a linear array of alternative HAMP and HAMP-like linker domains (poly-HAMP) in the N-terminal region. HAMP domains are quite common in prokaryotic histidine kinases where it mostly functions as signal transducer mediating conformational changes in the kinase domains. In contrast, poly-HAMP in HHK3 acts as a sensor and signal transducer to regulate histidine kinase activity. However, the mechanistic detail of this is poorly understood. Interestingly, recent studies indicate that the poly-HAMP-mediated regulation of the kinase activity varies among the orthologs. Hik1 is an important HHK3 ortholog from fungus Magnaporthe oryzae. In this paper, we aimed to decipher the role HAMP and HAMP-like linker domains in regulating the activity of Hik1p. We show that Hik1p acts as a bona fide osmosensor and negatively regulates the downstream HOG/p38 MAPK pathway in Saccharomyces cerevisiae. Our data suggest a differential role of the HAMP domains in the functionality of Hik1p. Most interestingly, the deletion of individual domains in poly-HAMP resulted in distinct active forms of Hik1p and thereby indicating that the poly-HAMP domain, instead of acting as on-off switch, regulates the histidine kinase activity by transition through multiple conformational states.
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http://dx.doi.org/10.1007/s00438-021-01809-7DOI Listing
September 2021

Clinical Measurement of Maximum Mouth Opening in Children Aged 6-12.

J Clin Pediatr Dent 2021 Jul;45(3):216-220

Objective: To evaluate the clinical maximum mouth opening in children and its correlation with age, and sex.

Study Design: Three hundred children of age 6-12 years, from different schools of Moradabad city were included. The participants were divided into three groups based on their age i.e Group 1 (n=100) 6-8 years, Group 2 (n=100) 8-10 years and Group 3 (n=100) 10-12 yrs. Three recordings of maximum mouth opening (MMO) were obtained using digital vernier caliper and the mean of three was considered as the MMO of that child. The data was analyzed using Spearman correlation, ANOVA with post- hoc Bonferroni test. The significance level was predetermined at p≤0.05 .

Results: The mean MMO for children of Moradabad of aged 6-8yrs in boys is 39.87 ± 4.91 mm and in girls is 36.85± 4.09 mm. In 8-10 yeas age group, the MMO in boys is 44.5± 5.1 mm and in girls 41.77± 5.24 mm. In 10-12 year age group, the MMO in boys is 49.63± 5.56 mm and in girls is 49.33±5.32 mm respectively. The MMO was found to be higher in boys in all the three age groups.

Conclusions: There was a significant difference in values of MMO in all the three age groups with boys having higher MMO values when compared to girls. Varying range of MMO values was observed within three age groups.
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http://dx.doi.org/10.17796/1053-4625-45.3.12DOI Listing
July 2021

Development and evaluation of [F]Flotaza for Aβ plaque imaging in postmortem human Alzheimer's disease brain.

Bioorg Med Chem Lett 2021 Aug 1;46:128164. Epub 2021 Jun 1.

Preclinical Imaging, Department of Radiological Sciences, University of California, Irvine 92697, USA. Electronic address:

Positron emission tomographic (PET) studies of amyloid β (Aβ) accumulation in Alzheimer's disease (AD) have shown clinical utility. The aim of this study was to develop and evaluate the effectiveness of a new fluorine-18 radiotracer [F]Flotaza (2-{2-[2-[F]fluoroethoxy]ethoxy}ethoxy)-4'-N,N-dimethylaminoazobenzene), for Aβ plaque imaging. Nucleophilic [F]fluoride was used in a one-step radiosynthesis for [F]flotaza. Using post mortem human AD brain tissues consisting of anterior cingulate (AC) and corpus callosum (CC), binding affinity of Flotaza, Ki = 1.68 nM for human Aβ plaques and weak (>10 M) for Tau protein. Radiosynthesis of [F]Flotaza was very efficient in high radiochemical yields (>25%) with specific activities >74 GBq/μmol. Brain slices from all AD subjects were positively immunostained with anti-Aβ. Ratio of [F]Flotaza in gray matter AC to white matter CC was >100 in all the 6 subjects. Very little white matter binding was seen. [F]Flotaza binding in AC strongly correlated with anti-Aβ immunostains. [F]Flotaza is therefore a suitable fluorine-18 PET radiotracer for PET imaging studies of human Aβ plaques.
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http://dx.doi.org/10.1016/j.bmcl.2021.128164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379902PMC
August 2021

Enzyme-Induced Supramolecular Order in Pyrene Dipeptide Hydrogels for the Development of an Efficient Energy-Transfer Template.

Biomacromolecules 2021 06 11;22(6):2393-2407. Epub 2021 May 11.

Institute of Nano Science and Technology, Phase-10, Sector-64, Mohali, Punjab 160062, India.

Peptide self-assembly is gathering much attention due to the precise control it provides for the arrangement of functional moieties for the fabrication of advanced functional materials. It is desirable to use a physical, chemical, or biological trigger that can control the self-assembly process. In the current article, we have applied an enzyme to induce the peptide self-assembly of an aromatic peptide amphiphile, which modulates the supramolecular order in the final gel phase material. We accessed diverse peptide hydrogels from identical gelator concentrations by simply changing the enzyme concentration, which controlled the reaction kinetics and influenced the dynamics of self-assembly. Depending upon the concentration of the enzyme, a bell-shaped relationship was observed in terms of intermolecular interactions, morphology, and properties of the final gel phase material. The access of non-equilibrium structures was further demonstrated by fluorescence emission spectroscopy, circular dichroism spectroscopy, atomic force microscopy, transmission electron microscopy, and rheology. This strategy is applied to construct a charge-transfer hydrogel by doping the donor hydrogel with an acceptor moiety, which exhibits efficient energy transfer. Interestingly, such structural control at the nanoscopic level can further tune the energy-transfer efficiency by simply modulating the enzyme concentration.
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http://dx.doi.org/10.1021/acs.biomac.1c00187DOI Listing
June 2021

Fungaemia due to rare yeasts in paediatric intensive care units: A prospective study.

Mycoses 2021 May 3. Epub 2021 May 3.

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

Background: Considering the emergence of fungaemia due to rare yeasts at our centre, we performed a systematic epidemiologic study on fungaemia due to rare yeasts.

Objectives: We undertook the present prospective observational study to explore the epidemiological features and clinical characteristics of fungaemia due to rare yeasts in paediatric ICUs at our centre.

Methods: The successive yeasts isolated from blood at our PICUs during December 2017 through March 2019 were identified by molecular methods. Fungaemia due to yeasts other than C. albicans, C. tropicalis, C. glabrata, C. krusei and C. parapsilosis was categorised as rare yeast fungaemia. Antifungal susceptibility testing of the yeast isolates was performed as per clinical and laboratory standards institute (CLSI) guidelines. We also compared different clinical parameters of fungaemia due to common versus rare yeasts, and rare yeasts in neonates versus non-neonates.

Results: During the study period, 212 yeast isolates were obtained from 159 patients at PICUs of our hospital, and 127 isolates from 98 patients (61.6%) were categorised as rare yeasts. Neonates acquired fungaemia significantly earlier after ICU admission than non-neonates (median: 4 vs 6 days; p = .005). of rare yeast fungaemia, Wickerhamomyces anomalus (43.8%) and Candida utilis (40.8%) were common isolates; surgical intervention and gastrointestinal disease were significantly associated; overall, azole, echinocandin and amphotericin B resistance was at 9.1%, 1.02% and 1.02%, respectively; overall mortality was 65.3%.

Conclusions: The emergence of rare yeasts especially W. anomalus and C. utilis causing fungaemia in our children demands urgent attention to control the spread.
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http://dx.doi.org/10.1111/myc.13297DOI Listing
May 2021

Towards decoding the coupled decision-making of metabolism and epithelial-to-mesenchymal transition in cancer.

Br J Cancer 2021 Jun 15;124(12):1902-1911. Epub 2021 Apr 15.

Center for Theoretical Biological Physics and Department of Physics, Northeastern University, Boston, MA, USA.

Cancer cells have the plasticity to adjust their metabolic phenotypes for survival and metastasis. A developmental programme known as epithelial-to-mesenchymal transition (EMT) plays a critical role during metastasis, promoting the loss of polarity and cell-cell adhesion and the acquisition of motile, stem-cell characteristics. Cells undergoing EMT or the reverse mesenchymal-to-epithelial transition (MET) are often associated with metabolic changes, as the change in phenotype often correlates with a different balance of proliferation versus energy-intensive migration. Extensive crosstalk occurs between metabolism and EMT, but how this crosstalk leads to coordinated physiological changes is still uncertain. The elusive connection between metabolism and EMT compromises the efficacy of metabolic therapies targeting metastasis. In this review, we aim to clarify the causation between metabolism and EMT on the basis of experimental studies, and propose integrated theoretical-experimental efforts to better understand the coupled decision-making of metabolism and EMT.
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http://dx.doi.org/10.1038/s41416-021-01385-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184790PMC
June 2021

Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry: Protocol standardisation, comparison and database expansion for faster and reliable identification of dermatophytes.

Mycoses 2021 Aug 25;64(8):926-935. Epub 2021 Apr 25.

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

Background: Accurate and early identification of dermatophytes enables prompt antifungal therapy. However, phenotypic and molecular identification methods are time-consuming. MALDI-TOF MS-based identification is rapid, but an optimum protocol is not available.

Objectives: To develop and validate an optimum protein extraction protocol for the efficient and accurate identification of dermatophytes by MALDI-TOF MS.

Materials/methods: Trichophyton mentagrophytes complex (n = 4), T. rubrum (n = 4) and Microsporum gypseum (n = 4) were used for the optimisation of protein extraction protocols. Thirteen different methods were evaluated. A total of 125 DNA sequence confirmed clinical isolates of dermatophytes were used to create and expand the existing database. The accuracy of the created database was checked by visual inspection of MALDI spectra, MSP dendrogram and composite correlation index matrix analysis. The protocol was validated further using 234 isolates.

Result: Among 13 protein extraction methods, six correctly identified dermatophytes but with a low log score (≤1.0). The modified extraction protocol developed provided an elevated log score of 1.6. Significant log score difference was observed between the modified protocol and other existing protocols (T. mentagrophytes complex: 1.6 vs. 0.2-1.0, p < .001; T. rubrum: 1.6 vs. 0.4-1.0, p < .001; M. gypseum:1.6 vs. 0.2-1.0, p < .001). Expansion of the database enabled the identification of all 234 isolates (73.5% with log score ≥2.0 and 26.4% with log scores range: 1.75-1.99). The results were comparable to DNA sequence-based identification.

Conclusion: MALDI-TOF MS with an updated database and efficient protein extraction protocol developed in this study can identify dermatophytes accurately and also reduce the time for identifying them.
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http://dx.doi.org/10.1111/myc.13285DOI Listing
August 2021

Subject Guided Eye Image Synthesis with Application to Gaze Redirection.

IEEE Winter Conf Appl Comput Vis 2021 Jan;2021:11-20

University of California, Santa Cruz.

We propose a method for synthesizing eye images from segmentation masks with a desired style. The style encompasses attributes such as skin color, texture, iris color, and personal identity. Our approach generates an eye image that is consistent with a given segmentation mask and has the attributes of the input style image. We apply our method to data augmentation as well as to gaze redirection. The previous techniques of synthesizing real eye images from synthetic eye images for data augmentation lacked control over the generated attributes. We demonstrate the effectiveness of the proposed method in synthesizing realistic eye images with given characteristics corresponding to the synthetic labels for data augmentation, which is further useful for various tasks such as gaze estimation, eye image segmentation, pupil detection, etc. We also show how our approach can be applied to gaze redirection using only synthetic gaze labels, improving the previous state of the art results. The main contributions of our paper are i) a novel approach for Style-Based eye image generation from segmentation mask; ii) the use of this approach for gaze-redirection without the need for gaze annotated real eye images.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040934PMC
January 2021

Role of flexible bronchoscopy in the diagnosis of invasive fungal infections.

Mycoses 2021 Jun 14;64(6):668-677. Epub 2021 Mar 14.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: There are sparse data on the role of flexible bronchoscopy (FB) in diagnosing invasive mould infections (IMIs).

Objective: To investigate the safety and usefulness of FB in IMI. We evaluate the factors associated with a successful diagnosis of IMI using FB. Further, we compare subjects of invasive pulmonary aspergillosis (IPA) with pulmonary mucormycosis (PM).

Methods: We retrospectively reviewed the clinical features, imaging data, bronchoscopy, microbiology and pathology details of subjects who underwent FB for suspected IMI. We categorised FB as diagnostic if it contributed to the diagnosis of IMI. We performed a multivariate analysis to identify the factors associated with a diagnostic bronchoscopy.

Results: Of the 3521 FB performed over 18 months, 132 (3.7%) were done for suspected IMIs. We included 107 subjects for the final analysis. The risk factors for IMI included renal transplantation (29.0%), diabetes (27.1%), haematological malignancy (10.3%) and others. We found bronchoscopic abnormalities in 33 (30.8%) subjects, and these were more frequent in those with confirmed PM (67%) than IPA (27%). IMI was confirmed in 79 (14 proven, 48 probable and 17 possible) subjects. FB was diagnostic in 71%. We experienced major complications in three cases (2.7%), including one death. On multivariate analysis, the visualisation of endobronchial abnormalities during FB (OR [95%, CI], 8.5 [1.4-50.4]) was the only factor associated with a diagnostic FB after adjusting for age and various risk factors.

Conclusions: Flexible bronchoscopy is a useful and safe procedure in diagnosing IMIs. The presence of endobronchial abnormalities predicts a successful diagnostic yield on FB.
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http://dx.doi.org/10.1111/myc.13263DOI Listing
June 2021

Scrutinizing the impact of water deficit in plants: Transcriptional regulation, signaling, photosynthetic efficacy, and management.

Physiol Plant 2021 Jun 31;172(2):935-962. Epub 2021 Mar 31.

Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.

Suboptimal availability of water limits plant growth, development, and performance. Drought is one of the leading factors responsible for worldwide crop yield reduction. In the future, owing to climate changes, more agricultural land will be affected by prolonged periods of water deficit. Thus, understanding the fundamental mechanism of drought response is a major scientific concern for improvement of crop production. To combat drought stress, plants deploy varied mechanistic strategies and alter their morphological, physiochemical, and molecular attributes. This helps plant to enhance water uptake and storage, reduce water loss and avoid wilting. Induction of several transcription factors and drought responsive genes leads to synthesis of stress proteins, regulation of water channels i.e. aquaporins and production of osmolytes that are essential for maintenance of osmotic balance at the cellular level. Self- and hormone-regulated signaling pathways are often stimulated by plants after receiving drought stress signals via secondary messengers, mitogen-activated protein kinases, and stress hormones. These signaling cascades often leads to stomatal closure and reduction in transpiration rates. Reduced carbon dioxide diffusion in chloroplast, lowered efficacy of photosystems, and other metabolic constraints limits the key regulatory photosynthetic process during water deficit. The impact of these stomatal and nonstomatal limitations varies with stress intensity, superimposed stresses and plant species. A clear understanding of the drought resistance process is thus important before adopting strategies for imparting drought tolerance in plants. These management practices at present include exogenous hormone application, breeding, and genetic engineering techniques for combating the water deficit issues.
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http://dx.doi.org/10.1111/ppl.13389DOI Listing
June 2021

Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature.

Mycopathologia 2021 May 5;186(2):289-298. Epub 2021 Feb 5.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, 160012, India.

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10-14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.
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http://dx.doi.org/10.1007/s11046-021-00528-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862973PMC
May 2021

Aspergillus fumigatus Skull Bone Osteomyelitis and Native Valve Endocarditis in a Young Boy: an Unusual Presentation of Chronic Granulomatous Disease.

J Clin Immunol 2021 05 16;41(4):814-816. Epub 2021 Jan 16.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1007/s10875-020-00939-8DOI Listing
May 2021

Hypochlorite-induced aggregation of fibrinogen underlies a novel antioxidant role in blood plasma.

Redox Biol 2021 04 30;40:101847. Epub 2020 Dec 30.

Flinders Health and Medical Research Institute and College of Medicine and Public Health, Flinders University, Bedford Park, Australia. Electronic address:

Fibrinogen, a major constituent of blood plasma, is highly susceptible to reaction with biological oxidants. It has been proposed that fibrinogen plays a role in antioxidant defence, but oxidation of fibrinogen is also known to disrupt normal blood clotting and is implicated in the pathology of atherosclerosis. In the present study, we show that the biological oxidant hypochlorite promotes the formation of soluble high molecular weight fibrinogen assemblies ≥40 × 10 Da, that do not accumulate when fibrinogen is induced to aggregate by other stresses such as heating or hydroxyl-mediated damage in vitro. Hypochlorite-modified fibrinogen is stable at 37 °C as assessed by precipitation assays, and has reduced susceptibility to iron-induced (hydroxyl-mediated) precipitation compared to native fibrinogen. In contrast to hypochlorite-modified albumin, which is known to be immunostimulatory, hypochlorite-modified fibrinogen does not induce RAW 264.7 (macrophage-like) cells or EOC 13.31 (microglia-like) cells to produce reactive oxygen species or induce cell death. Furthermore, depletion of fibrinogen from human blood plasma increases the immunostimulatory property of blood plasma after it is supplemented with hypochlorite in situ. We propose that reaction of hypochlorite with fibrinogen in blood plasma potentially reduces the accumulation of other hypochlorite-modified species such as immunostimulatory hypochlorite-modified albumin. The latter represent a novel role for fibrinogen in blood plasma antioxidant defence.
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http://dx.doi.org/10.1016/j.redox.2020.101847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808953PMC
April 2021

Rapid and Simple Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method for Simultaneous Quantifications of Triazole Antifungals in Human Serum.

Mycopathologia 2021 Mar 3;186(1):27-39. Epub 2021 Jan 3.

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

Purpose: To develop and validate a one-step, rapid and simple reversed-phase high-performance liquid chromatography (HPLC)-based protocol for the simultaneous measurement of voriconazole (VCZ), posaconazole (POSA), itraconazole (ITC) in serum/plasma.

Methods: Calibration standards (CS) and quality control samples were prepared in drug-free serum by spiking with the triazoles at different concentrations. HPLC was performed with C column, isocratic mobile phase after extraction with cold acetonitrile. The standardized method was tested in 2693 patients' serum/plasma samples.

Results: Linearity of CS for ITC, VCZ and POSA was proportional to the nominal concentration (correlation coefficient > 0.999). Limit of detection (mg/L) for ITC, VCZ and POSA was 0.25, 0.25 and 0.125, respectively. The lower limit of quantification (mg/L) for ITC, VCZ and POSA was 0.5, 0.5 and 0.25, respectively. Precision and accuracy were in acceptable range with 100% average percentage recovery. No interferences from endogenous substances and other antimicrobial compounds were noted. In clinical samples, the therapeutic range achieved for VCZ was 39.9%. Whereas, 61.1% and 44% of samples with ITC and POSA, respectively, were in the sub-therapeutic range.

Conclusion: We developed a rapid and simple HPLC method to quantify common triazoles in a single chromatographic run allowing simultaneous measurement of different antifungals in a small volume of serum/plasma. Thus, therapeutic drug monitoring requests can be processed in one run without changing the protocol parameters, column or column conditioning thereby improving turnaround time.
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http://dx.doi.org/10.1007/s11046-020-00514-0DOI Listing
March 2021

Molecular identification of pathogenic fungi in formalin-fixed and paraffin-embedded tissues.

J Med Microbiol 2021 Feb;70(2)

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

Histopathological examination (HPE) of tissue helps in the diagnosis of invasive fungal infections (IFIs) but cannot identify the fungus to the genus/species level Available protocols for the molecular identification of fungi from formalin-fixed and paraffin-embedded (FFPE) tissues have limitations in terms of extraction and target selection, and standardisation. Development of sequence-based fungal identification protocol after extraction of DNA from formalin-fixed and paraffin-embedded (FFPE) tissues. A total of 63 FFPE tissues from histopathology proven IFI cases were used to standardize the DNA extraction (commercial QIAamp kit-based extraction and conventional phenol-chloroform-isoamyl alcohol [PCI] method) and sequence-based fungal identification protocols. The PCR targeted different ribosomal DNA (rDNA) regions including complete internal transcribed spacer (ITS1-5.8S-ITS2), separate ITS1 and ITS2, 18S and D1/D2 of 28S regions. Semi-nested PCR targeting Mucorales-specific 18S rDNA region was performed in tissues having aseptate hyphae. The optimized ITS1-PCR protocol was evaluated in 119 FFPE tissues containing septate hyphae or yeast, and Mucorales-specific semi-nested PCR in 126 FFPE tissues containing aseptate hyphae. The DNA yield by conventional PCI method was significantly higher (<0.0001) than commercial kit, though the quality of DNA was similar by both protocols. The test accuracy was best while using ITS1 (61.9 %) as the target compared to 7.9, 29.9 and 22.2 % on targeting ITS1-5.8S-ITS2, ITS2, the D1/D2 region of 28S, respectively. The test accuracies of ITS1-PCR in tissues containing septate hyphae, aseptate hyphae and yeasts were 75.5, 18.7 and 100 %, respectively. The amplification (targeting ITS1 region) improved by increasing the thickness of tissue section (up to 50 µm) used for DNA extraction. ITS1-PCR protocol could amplify fungal DNA in 76 (63.8 %) tissues and Mucorales-specific semi-nested PCR in 86 (68.3 %) tissues. Conventional PCI-based DNA extraction from thick tissue (50 µm) may be used until optimal commercial fungal DNA extraction kit is developed. Subsequent ITS1-PCR for septate fungi and yeast, and semi-nested PCR targeting 18S rDNA for Mucorales are recommended to identify the fungus in FFPE tissues.
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http://dx.doi.org/10.1099/jmm.0.001282DOI Listing
February 2021

A Selective Medium for Isolation and Detection of Candida auris, an Emerging Pathogen.

J Clin Microbiol 2021 01 21;59(2). Epub 2021 Jan 21.

Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Identification of is challenging and requires molecular or protein profiling-based approaches, availability of which is limited in many routine diagnostic laboratories, necessitating the development of a cost-effective, rapid, and reliable method of identification. The objective of this study was to develop a selective medium for identification. Eighteen and 30 non- yeasts were used for the standardization of the selective medium. Sodium chloride (10% to 13% concentration) and ferrous sulfate (8 mM to 15 mM) were added to yeast extract-peptone-dextrose (YPD) agar in various combinations followed by incubation at 37°C, 40°C, or 42°C for 2 to 3 days. For validation, 579 yeast isolates and 40 signal-positive Bactec blood culture (BC) broths were used. YPD agar comprising 12.5% NaCl and 9 mM ferrous sulfate incubated at 42°C for 48 h, named Selective Auris Medium (SAM), allowed selective growth of A total of 95% (127/133) of isolates tested grew on the standardized media within 48 h, and the remaining 6 isolates grew after 72 h, whereas the growth of 446 non- yeast isolates was completely inhibited. The specificity and sensitivity of the test medium were both 100% after 72 h of incubation. The positive and negative predictive values were also noted to be 100% after 72 h of incubation. The formulated selective medium can be used for the detection and identification of The SAM is inexpensive, can easily be prepared, and can be used as an alternative to molecular diagnostic tools in the clinical microbiology laboratory.
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http://dx.doi.org/10.1128/JCM.00326-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111121PMC
January 2021

Pathway-Dependent Preferential Selection and Amplification of Variable Self-Assembled Peptide Nanostructures and Their Biological Activities.

ACS Appl Mater Interfaces 2020 Nov 15;12(47):52445-52456. Epub 2020 Nov 15.

Institute of Nano Science and Technology, Phase-10, Sector-64, Mohali, Punjab 160062, India.

We demonstrate the formation of diverse peptide nanostructures, which are "out of equilibrium" based on a single dipeptide gelator. These structures represent the differential energy states of the free energy landscape, which are accessed by differential energy inputs provided by variable self-assembly pathways, that is, heat-cool method or ultrasonication. A higher energy input by the heat-cool method created a thermodynamically favored long entangled nanofibrillar network, while twisted ribbonlike structures were prevalent by ultrasonication. Interestingly, the nanofibrillar network representing the global thermodynamic minima could be accessed by simply melting the kinetically trapped structures as indicated by the thermoreversibility studies. The impact on the material strength was remarkable; gels with an order of magnitude difference in mechanical properties could be fabricated by simply modulating the self-assembly pathways. Interestingly, the thermodynamically favored nanofibrous network promoted cellular adhesion and survival, while a significant number of cells fail to adhere on the kinetically trapped twisted ribbons. Thus, nonequilibrium nanostructures open up new directions to develop advanced functional materials with diverse functions.
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http://dx.doi.org/10.1021/acsami.0c16725DOI Listing
November 2020
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