Publications by authors named "Nidhi Sharma"

226 Publications

Single-cell resolution of lineage trajectories in the Arabidopsis stomatal lineage and developing leaf.

Dev Cell 2021 Apr;56(7):1043-1055.e4

Department of Biology, Stanford University, Stanford, CA 94305-5020, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305-5020, USA. Electronic address:

Dynamic cell identities underlie flexible developmental programs. The stomatal lineage in the Arabidopsis leaf epidermis features asynchronous and indeterminate divisions that can be modulated by environmental cues. The products of the lineage, stomatal guard cells and pavement cells, regulate plant-atmosphere exchanges, and the epidermis as a whole influences overall leaf growth. How flexibility is encoded in development of the stomatal lineage and how cell fates are coordinated in the leaf are open questions. Here, by leveraging single-cell transcriptomics and molecular genetics, we uncovered models of cell differentiation within Arabidopsis leaf tissue. Profiles across leaf tissues identified points of regulatory congruence. In the stomatal lineage, single-cell resolution resolved underlying cell heterogeneity within early stages and provided a fine-grained profile of guard cell differentiation. Through integration of genome-scale datasets and spatiotemporally precise functional manipulations, we also identified an extended role for the transcriptional regulator SPEECHLESS in reinforcing cell fate commitment.
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http://dx.doi.org/10.1016/j.devcel.2021.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054824PMC
April 2021

Tuning self-renewal in the Arabidopsis stomatal lineage by hormone and nutrient regulation of asymmetric cell division.

Elife 2021 03 19;10. Epub 2021 Mar 19.

Department of Biology, Stanford University, Stanford, United States.

Asymmetric and self-renewing divisions build and pattern tissues. In the Arabidopsis stomatal lineage, asymmetric cell divisions, guided by polarly localized cortical proteins, generate most cells on the leaf surface. Systemic and environmental signals modify tissue development, but the mechanisms by which plants incorporate such cues to regulate asymmetric divisions are elusive. In a screen for modulators of cell polarity, we identified , a negative regulator of ethylene signaling. We subsequently revealed antagonistic impacts of ethylene and glucose signaling on the self-renewing capacity of stomatal lineage stem cells. Quantitative analysis of cell polarity and fate dynamics showed that developmental information may be encoded in both the spatial and temporal asymmetries of polarity proteins. These results provide a framework for a mechanistic understanding of how nutritional status and environmental factors tune stem-cell behavior in the stomatal lineage, ultimately enabling flexibility in leaf size and cell-type composition.
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http://dx.doi.org/10.7554/eLife.63335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009662PMC
March 2021

Pb sensing by coumarin sulphonamide hybrids in aqueous medium.

Luminescence 2021 Mar 13. Epub 2021 Mar 13.

Food and Nutraceutical Division, CSIR - Institute of Himalayan Bioresource Technology, Palampur, India.

Metals play an important role in various metabolic activities in the human body, but above desired concentrations, a role reversal occurs that causes deadly outcomes viz., cancer. Metals cannot be cracked down and are non-biodegradable. It is the bioaccumulation of toxic metals inside the biomatrices, that further intensifies the research on different means of metal detoxification from different matrices. Among heavy toxic metals lead is a brutal carcinogen that requires pitiless sensors for its capturing. The use of heterocycles for metal sensing in supramolecular chemistry is preferred due to the strong chelation they offer to toxic metals. The C1-C3 probes were synthesized and studied for their Pb binding ability. All the probes were prepared by treating bromoacetyl coumarin with camphor sulphonamide, 5-dimethylamino-1-naphthalene sulphonamide, and methyl-2-amino-sulphonyl benzoate at room temperature. The probes show selective binding with Pb ions in aqueous acetonitrile among different tested metal ions viz., Cu , Zn , Ni , Mn and Pb ions as shown in ultraviolet (UV)-visible, nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC) studies. These sulphur-containing probes bind very well with Pb ions by offering selectivity in binding positions that capture lead ions at their minimum possible concentration.
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http://dx.doi.org/10.1002/bio.4042DOI Listing
March 2021

Dysregulation of SIRT-1 Signaling in Multiple Sclerosis and Neuroimmune Disorders: A Systematic Review on SIRTUIN Activators as Potential Immunomodulators and Influences on other Dysfunctions.

Endocr Metab Immune Disord Drug Targets 2021 Mar 8. Epub 2021 Mar 8.

Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab. India.

Immune dysregulation, neuronal inflammation, and oligodendrocyte degradation are key causes for autoimmune disorders like multiple sclerosis (MS) and various otherimmune dysregulated neurodegenerative complications responsible for CNS-mediated immune responses.Sirtuins (SIRT-1) is nicotinamide adenosine dinucleotide (NAD)-dependent transcriptional protein thatdeacetylases and removes acetyl groups from its transcription factors like P53, FOXO, NF-Κb, PGC-1α. SIRT-1 mediates a wide range of physiological functions,including gene transcription, metabolism, neuronal apoptosis, and glucose production.SIRT-1 dysregulation targets transcription factors,and other molecular alterations such as gene expression modification influence neuronal plasticity, inhibits Th17 cells, and interleukin-1β can aggravate brain diseases.Preclinical and clinical findings show that the upregulation of SIRT-1 reduces autoimmunity, neurodegeneration, and neuroexcitation. Even though drugs are being developed for symptomatic therapies in clinical trials, there are particular pharmacological implications for improving post-operative conditions in neurodegenerativepatients where intensive care is required.Understanding the SIRT-1 signaling and identifying immune-mediated neuron deterioration can detect major therapeutic interventions that could prevent neurocomplications.Thus, in the current review, we have addressed the manifestations of disease by the downregulation of SIRT-1 that could potentially cause MS and other neurodegenerative disorders and provided data on existing available and effective drug therapies and disease management strategies.
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http://dx.doi.org/10.2174/1871530321666210309112234DOI Listing
March 2021

Role of Stem Cell Transplantation in Multiple Myeloma.

Cancers (Basel) 2021 Feb 18;13(4). Epub 2021 Feb 18.

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center Columbus, Columbus, OH 43210, USA.

Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs. Tandem auto-SCT followed by maintenance has shown a progression-free survival (PFS) benefit in high-risk MM, and hence can be considered in young and fit patients with high-risk disease. Auto-SCT has the advantages of resetting the bone marrow microenvironment, short-lived toxicity compared to the long-term physical and financial toxicities of continued chemotherapy in the absence of SCT, very low transplant-related mortality (TRM) in high volume centers, and providing longer disease-free survival when followed by maintenance therapy. Allogeneic SCT is one potentially curative option for MM, albeit with an increased risk of death due to high TRM. Strategies to modulate the graft-versus-host disease (GVHD) while maintaining or improving the graft-versus-myeloma (GVM) effect could place allogeneic SCT back in the treatment armamentarium of MM.
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http://dx.doi.org/10.3390/cancers13040863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922596PMC
February 2021

Connection between JAK/STAT and PPARγ signaling during the progression of multiple sclerosis: Insights into the modulation of T-cells and immune responses in the brain.

Curr Mol Pharmacol 2021 Mar 1. Epub 2021 Mar 1.

Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab. India.

Multiple Sclerosis (MS) is a severe brain and spinal cord condition with a diverse autoimmune response and a wide variety of demyelination symptoms that primarily affect young adults. The primary reason for this disease is inflammation of white and grey matter caused by increased production of proinflammatory cytokines, which further damages the progenitor oligodendrocytes and appears to induce hypertrophy of the astrocytes and gliosis. Overexpression of the JAK/STAT signaling pathway contributes directly to physiological and pathological results in motor neuron diseases. Cytokines such as IL-17, IL-6, IL-12, TNF-α, and INF-ϒ use JAK/STAT signaling to trigger self-reactive CD4+ T-cells differentiate them into Th1 phenotypes that over-activate immune reactions in the brain. Similarly, PPARγ plays a critical role in regulating the immune response by providing an anti-inflammatory effect by inhibiting macrophage and cytokine production activation. PPARγ also mediates the intrinsic molecular process of the T-cell, which selectively regulates the differentiation of Th17. Various studies indicate the neuroprotective function of PPARγ agonists by attenuating the JAK/STAT mediated activation of glial cells, inhibiting interleukin, and the differentiation of Th1 cells. Therefore, to maintain the brain's immune system, both PPARγ,and JAK/STAT oppositely regulate each other. Dysregulation in JAK/STAT and PPARγ signaling contributes to several physiological changes leading to neurological disorders, including MS. Based on the above view; we summarized the combined role of JAK/STAT-PPARγsignaling in MS and explored potential therapeutic strategies for disease improvement by the use of pathway modulators.
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http://dx.doi.org/10.2174/1874467214666210301121432DOI Listing
March 2021

Guggulsterone ameliorates ethidium bromide-induced experimental model of multiple sclerosis via restoration of behavioral, molecular, neurochemical and morphological alterations in rat brain.

Metab Brain Dis 2021 Jun 26;36(5):911-925. Epub 2021 Feb 26.

Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.

Multiple Sclerosis (MS) is a progressive neurodegenerative disease with clinical signs of neuroinflammation and the central nervous system's demyelination. Numerous studies have identified the role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) overexpression and the low level of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in MS pathogenesis. Guggulsterone (GST), an active component derived from 'Commiphora Mukul,' has been used to treat various diseases. Traditional uses indicate that GST is a suitable agent for anti-inflammatory action. Therefore, we assessed the therapeutic potential of GST (30 and 60 mg/kg) in ethidium bromide (EB) induced demyelination in experimental rats and investigated the molecular mechanism by modulating the JAK/STAT and PPAR-γ receptor signaling. Wistar rats were randomly divided into six groups (n = 6). EB (0.1%/10 μl) was injected selectively in the intracerebropeduncle (ICP) region for seven days to cause MS-like manifestations. The present study reveals that long-term administration of GST for 28 days has a neuroprotective effect by improving behavioral deficits (spatial cognition memory, grip, and motor coordination) associated with lower STAT-3 levels. While elevating PPAR-γ and myelin basic protein levels in rat brains are consistent with the functioning of both signaling pathways. Also, GST modulates the neurotransmitter level by increasing Ach, dopamine, serotonin and by reducing glutamate. Moreover, GST ameliorates inflammatory cytokines (TNF, IL-1β), and oxidative stress markers (AchE, SOD, catalase, MDA, GSH, nitrite). In addition, GST prevented apoptosis, as demonstrated by the reduction of caspase-3 and Bax. Simultaneously, Bcl-2 elevation and the restoration of gross morphology alterations are also recovered by long-term GST treatment. Therefore, it can be concluded that GST may be a potential alternative drug candidate for MS-related motor neuron dysfunctions.
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http://dx.doi.org/10.1007/s11011-021-00691-xDOI Listing
June 2021

Hypercalcemia of Malignancy: An Incidental Finding in Carcinoma Cervix.

Indian J Palliat Care 2020 Oct-Dec;26(4):548-550. Epub 2020 Nov 19.

Department of Radiation Oncology, AIIMS, Rishikesh, Uttarakhand, India.

Hypercalcemia occurs in 30% of patients of cancer at either as apart of paraneoplastic process or due to bone metastases. It is an uncommon finding in gynecological cancers. Most common in ovarian cancers and till date very few cancer cervix with hypercalcemia have been reported. We, hereby, report patient of carcinoma cervix who was found to have incidental hypercalcemia without any associated clinical symptoms.
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http://dx.doi.org/10.4103/IJPC.IJPC_220_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888430PMC
November 2020

Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation.

Cancers (Basel) 2021 Feb 4;13(4). Epub 2021 Feb 4.

Comprehensive Cancer Center Columbus, Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II-IV at TAC level ≥10.15 ng/mL ( = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse ( = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL ( = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.
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http://dx.doi.org/10.3390/cancers13040613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913846PMC
February 2021

Letter to the editor - Transcranial direct current stimulation improves quality of life and physical fitness in diabetic polyneuropathy: a pilot double blind randomized controlled trial".

J Diabetes Metab Disord 2020 Dec 6;19(2):2025-2026. Epub 2020 Sep 6.

Department of Musculoskeletal Physiotherapy, Maharishi Markandeshwar Institute of Physiotherapy and Rehabilitation, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207 India.

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http://dx.doi.org/10.1007/s40200-020-00621-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843740PMC
December 2020

Dopamine induces functional extracellular traps in microglia.

iScience 2021 Jan 6;24(1):101968. Epub 2021 Jan 6.

Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan 342037, India.

Dopamine (DA) plays many roles in the brain, especially in movement, motivation, and reinforcement of behavior; however, its role in regulating innate immunity is not clear. Here, we show that DA can induce DNA-based extracellular traps in primary, adult, human microglia and BV2 microglia cell line. These DNA-based extracellular traps are formed independent of reactive oxygen species, actin polymerization, and cell death. These traps are functional and capture fluorescein (FITC)-tagged even when reactive oxygen species production or actin polymerization is inhibited. We show that microglial extracellular traps are present in . This is crucial because cells are known to secrete DA. Our findings demonstrate that DA plays a significant role in sterile neuro-inflammation by inducing microglia extracellular traps.
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http://dx.doi.org/10.1016/j.isci.2020.101968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797945PMC
January 2021

Human ankyrins and their contribution to disease biology: An update.

J Biosci 2020 ;45

Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab 151401, India.

Ankyrins are ubiquitously expressed proteins that play a critical role in the integrity of cytoskeleton and cellular signalling. Their presence in metazoans and evolutionary conserved protein primary sequence indicates their functional significance. Tissue-specific isoforms and an array of transcript variants make this protein one of the indispensable cellular components. Membrane-binding domains consist of ankyrin repeats that bind with several functional membrane proteins that enable maintaining cellular integrity. Cytosolic ankyrins help in cellular signal transduction. Linkage studies and recent genome-wide association studies uncovered the pathogenic roles of ankyrins (ankyrin-R, ankyrin-B and ankyrin-G) in several diseases, such as hereditary spherocytosis, long QT syndrome, intellectual disability, and CRASH syndrome, among several others. Identification of in celiac disease may potentially explain the link between neuronal health and immunity. It is thus warranted to investigate the role of neuronal factors in immune diseases and vice versa. In this review, we briefly discussed the contribution of ankyrin genes to human diseases.
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January 2020

AL amyloidosis: The effect of fluorescent in situ hybridization abnormalities on organ involvement and survival.

Cancer Med 2021 02 21;10(3):965-973. Epub 2020 Dec 21.

Division of Hematology, Department. of Internal Medicine, The Ohio State University Comprehensive Cancer Center Columbus, OH, USA.

Background: Systemic light chain (AL) amyloidosis is a clonal plasma-cell neoplasm that carries a poor prognosis. Although AL amyloidosis and Multiple Myeloma (MM) can co-exist and share various cytogenetic chromosomal abnormalities, little is known about Fluorescent in situ hybridization (FISH) and its prognostic relevance in AL amyloidosis.

Aim: The study aims to evaluate the most prevalent FISH cytogenetic abnormalities in AL patients as independent prognostic factors, and assess the impact of cytogenetics on the survival of high-risk cardiac AL patients.

Materials & Methods: This retrospective study reviewed 113 consecutive AL patients treated at The Ohio State University (OSU). Patients were divided into subgroups based on FISH data obtained within 90 days of diagnosis. Hyperdiploidy was defined as trisomies of at least 2 chromosomal loci. Primary endpoints were progression free survival (PFS) and overall survival (OS). Kaplan Meier curves were used to calculate PFS and OS. The log-rank test and Cox proportional hazard models were used to test the equality of survival functions and further evaluate the differences between groups.

Results: FISH abnormalities were detected in 76% of patients. Patients with abnormal FISH trended toward lower overall survival (OS) (p=0.06) and progression free survival (PFS) (p=0.06). The two most prevalent aberrations were translocation t(11;14) (39%) and hyperdiploidy-overall (38%). Hyperdiploidy-overall was associated with worsening PFS (p=0.018) and OS (p=0.03), confirmed in multivariable analysis. Patients with del 13q most frequently had cardiac involvement (p=0.006) and was associated with increased bone marrow plasmacytosis (p=0.02). Cardiac AL patients with no FISH abnormalities had much improved OS (p=0.012) and PFS (p=0.018) CONCLUSIONS: Our findings ultimately reveal the association of hyperdiploidy on survival in AL amyloidosis patients, including the high-risk cardiac AL population.
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http://dx.doi.org/10.1002/cam4.3683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897960PMC
February 2021

Optimizing pediatric peripheral blood stem cell collection.

Transfus Apher Sci 2021 Feb 8;60(1):102966. Epub 2020 Oct 8.

Bone Marrow Transplant Unit, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India.

Introduction: Pediatric PBSC harvests pose specific challenges during apheresis and a knowledge of the same and variables affecting PBSC collection are very important in planning these procedures. In the present study safety profile of pediatric PBSC procedures and variables influencing the successful collection were analyzed.

Method: Pediatric PBSC harvest data for 3 years was reviewed for donor, procedural and product parameters and any specific challenges faced during the procedures. Successful PBSC collection was defined when CD34 dose obtained was ≥2 × 10 cells/Kg of recipients' body weight.

Results: 85 PBSC collections performed on 46 children (age range 1.5-15 years) were included. Sixty-two procedures were on autologous donors and 23 on allogenic donors. The median CD34+ cell dose in the PBSC product per procedure was 2.12 × 10 cells/Kg for autologous procedures and 4.6 × 10 cells/Kg for allogenic procedures. Systemic adverse reaction was observed during only one procedure (0.01 %) and was managed conservatively. Successful dose was collected in 52 procedures (61.17 %) and was significantly associated with CD34+ count of more than 19.7/μL, monocyte count of more than 1.65 × 10/μL, allogenic collection and female gender (p = 0.00001, p = 0.011, p = 0.00052, and p = 0.0001, respectively).

Conclusion: PBSC collection is safe in pediatric age groups and pre-procedure CD34 count of ≥20/μL on the day of collection may result in successful collection of stem cell dose. It is important to identify factors associated with failed collection for appropriate counselling and justifying pre-emptive use of stem cell mobilizing agents.
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http://dx.doi.org/10.1016/j.transci.2020.102966DOI Listing
February 2021

The Effectiveness of Non-Benzodiazepine, Non-Barbiturate Medications for Alcohol Withdrawal Syndrome: A Rapid Systematic Review.

Alcohol Alcohol 2020 Dec 3. Epub 2020 Dec 3.

Drug De-addiction and Treatment Centre, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Madhya Marg, Sector 12 Chandigarh 160012, India.

Aim: There are potential clinical, ethical and legal concerns with overdosing benzodiazepines (or barbiturates) for the treatment of moderate to severe alcohol withdrawal symptoms (AWS) through telemedicine or ambulatory outpatients. A rapid systematic review to (a) qualitatively summarize the non-benzodiazepine treatment alternatives, (b) evaluate the quality of evidence for the same to effectively manage moderate to severe AWS.

Methods: We conducted searches on PubMed (January 1990 to 31 March 2020), Cochrane Central Register of Controlled Trials, and Google Scholar. We selected the English language randomized controlled trials (RCTs) assessing the efficacy and adverse effects of non-benzodiazepine and non-barbiturate medications among adults with a diagnosis of AWS. Data extraction was done in a predefined format. Risk of bias (RoB) assessment and qualitative synthesis of evidence was done with the RoB2 tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) proGDT.

Results: Thirty-four RCTs were included. Gabapentin (n = 6), carbamazepine (n = 5), baclofen (n = 5), valproate (n = 3), clonidine/lofexidine (n = 3) and acamprosate (n = 2) had more than one trial with a particular comparison group. Four studies were found to have a low ROB. The GRADE evidence summary showed gabapentin had a 'moderate' level of evidence against standard benzodiazepine treatments for reducing the severity of AWS. The level of certainty was 'low' for carbamazepine, baclofen and valproate and 'very low' for acamprosate and clonidine/lofexidine. Reported adverse events between these alternative medications and benzodiazepines or placebo were generally unremarkable.

Conclusions: Although benzodiazepines remain the treatment of choice for AWS, during particular circumstances, gabapentin could be an alternative although like benzodiazepines is not without risk when used in the community. Future RCTs must aim to improve upon the quality of evidence.
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http://dx.doi.org/10.1093/alcalc/agaa125DOI Listing
December 2020

AL Amyloidosis: The Effect of Maintenance Therapy on Autologous Stem Cell Transplantation Outcomes.

J Clin Med 2020 Nov 23;9(11). Epub 2020 Nov 23.

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.

Background: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic light chain (AL) amyloidosis. While maintenance post ASCT in multiple myeloma is now standard, the decision to utilize maintenance in AL amyloidosis remains largely unexplored. The present study aims to determine the prognostic significance of utilizing maintenance therapy following ASCT and assess the impact of fluorescent in situ hybridization (FISH) abnormalities, bone marrow plasma cell burden (BMPC), and degree of organ involvement on this decision.

Methods And Results: This is a retrospective analysis of fifty AL amyloidosis patients who underwent ASCT at The Ohio State University. Twenty-eight patients received maintenance and twenty-two did not. Kaplan-Meier survival analysis was used to compare the effect of maintenance therapy with no significant difference in PFS ( = 0.66) and OS ( = 0.32) between the two groups. There was no difference in survival based on maintenance when further categorized by FISH, PFS ( = 0.15), and OS ( = 0.65); BMPC ≥ 10%, PFS ( = 0.49), and OS ( = 0.32); or with 2 or more organs involved, PFS ( = 0.34) and OS ( = 0.80).

Conclusion: Maintenance therapy post ASCT did not impact PFS or OS when categorized by FISH abnormalities, increasing BMPC, or ≥2 organs involved in AL amyloidosis patients.
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http://dx.doi.org/10.3390/jcm9113778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700492PMC
November 2020

Multiple Myeloma: Clinical Updates from the American Society of Clinical Oncology Annual Scientific Symposium 2020.

J Clin Med 2020 Nov 11;9(11). Epub 2020 Nov 11.

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.

The novel clinical data for plasma cell neoplasms (smoldering myeloma, multiple myeloma, and AL amyloidosis) that were presented in the 2020 American Society of Clinical Oncology virtual scientific symposium are summarized here. Data from large phase-3 studies (CASSIOPEIA, ENDURANCE, and TOURMALINE-MM4 trials) and phase-2 studies (SWOG 1211, GMMG CONCEPT trials) for newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplantation are described. Updates from previous important studies for multiple myeloma (STaMINA) along with studies on three different chimeric antigen receptor (CAR-) T cell products are also described. Results of clinical studies involving the use of anti-myeloma drugs with novel mechanisms of action such as immunoconjugates, selinexor, venetoclax, monoclonal antibodies, and data on minimal residual disease (MRD) are discussed. These data provide an overview of the efficacy and safety of the various treatments in multiple myeloma and could lead to changes in our clinical practice, which could pave the path for a "cure" in myeloma.
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http://dx.doi.org/10.3390/jcm9113626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697517PMC
November 2020

Impact of COVID - 19 on mental health and physical load on women professionals: an online cross-sectional survey.

Health Care Women Int 2020 Nov-Dec;41(11-12):1255-1272. Epub 2020 Oct 6.

Department of Cardiopulmonary Physiotherapy, Maharishi Markandeshwar Institute of Physiotherapy and Rehabilitation, Maharishi Markandeshwar (Deemed to be University), Ambala, Haryana, India.

In December, 2019, a pathogen was identified and named as 2019 novel coronavirus (2019-nCoV). To prevent its spread, lockdowns were announced and working women had to perform dual roles: work from home and work for home. In the present study researchers aimed to assess mental and physical load on Indian women professionals during lockdown due to COVID-19. An online cross-sectional survey was carried out using a Google form. The questionnaire consisted of queries based on following domains: demographic details, awareness of COVID-19 pandemic, analysis of mental health of participants during lockdown, estimate of physical load for work from home, physical load due to house hold chores and overall effect on health. The sample was collected from 28 April to 12 May 2020 and 537 responses were recorded from women working from home as well as working for home through snowball sampling technique. Mental health was moderately and severely affected in 27.5% and 27% of participants respectively. 34.3% experienced great increase in physical load due to house hold chores during lockdown. 45.81% reported pain in neck and back region with 36.31% participants reported strain in their eyes sometimes. 15.08% and 8.37% had a tendency to over react in the present situation often and always respectively. The women performing work from home and work for home during the lock down are going through moderately increased physical and mental load. Their health is also affected by development of musculoskeletal problems.
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http://dx.doi.org/10.1080/07399332.2020.1825441DOI Listing
March 2021

Post Traumatic calcinosis cutis of eyelid.

Nepal J Ophthalmol 2019 Jul;11(22):215-217

Department of Ophthamology, Indira Gandhi ESI hospital, Jhilmil. New Delhi.

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http://dx.doi.org/10.3126/nepjoph.v11i2.27830DOI Listing
July 2019

Letter to Editor "Effects of handwriting exercise on functional outcome in Parkinson disease: A randomized controlled trial".

J Clin Neurosci 2020 09 7;79:277-278. Epub 2020 Aug 7.

University Research Fellow, Maharishi Markandeshwar Institute of Physiotherapy and Rehabilitation, Maharishi Markandeshwar (deemed to be University), Mullana, Ambala, Haryana 133207, India. Electronic address:

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http://dx.doi.org/10.1016/j.jocn.2020.06.020DOI Listing
September 2020

Repurposing of auranofin against bacterial infections: An In silico and In vitro study.

Curr Comput Aided Drug Des 2020 Jul 17. Epub 2020 Jul 17.

Department of Pharmacology, ISF College of Pharmacy (ISFCP), Moga, Punjab. India.

Aim: The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent.

Methods: In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software).

Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate multimodal mechanism of action of auranofin. Finally, MTT assay has shown non-cytotoxic effect of auranofin.

Conclusion: In conclusion, auranofin in combination with existing antibiotics could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides possibility of use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.
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http://dx.doi.org/10.2174/1386207323666200717155640DOI Listing
July 2020

A Prospective, Randomized, Interventional Study of Oral Iron Supplementation Comparing Daily Dose with Alternate Day Regimen Using Hepcidin as a Biomarker in Iron Deficiency Anemia.

J Assoc Physicians India 2020 May;68(5):39-41

Senior Resident, Department of Medicine, SMS Medical College, Jaipur, Rajasthan.

Aim: To assess effect of daily vis-a-vis alternate day oral iron therapy in terms of hemoglobin, reticulocyte hemoglobin equivalent (RET-He) and GI side effects using hepcidin as a biomarker.

Methods: A hospital based randomized interventional two-arm analytical study was done among patients of IDA (20 in each group). The study population was divided into two groups by randomisation. Group 1 received oral iron supplements on alternate day and Group 2 received iron supplements daily. Hemoglobin, RET-He, Serum ferritin and Hepcidin level were assessed.

Results: On day 2nd, the rise in Hepcidin was not significant from base line in alternate day therapy group but was significantly increased in daily therapy group. On day 3, the rise in hepcidin was significant from base line in both the groups but the mean change in hepcidin was more in daily therapy group. RET-He began increasing on day 2nd in both the groups. In alternate day therapy group, the rise in RET-He was significant from base line from the day 2nd onwards while the rise in RET-He in daily therapy group was not significant even on day 3. In alternate day iron therapy group, the mean increase in hemoglobin on day 21th (1.58 ±0.53 gm/dl) was significantly more than mean increase among daily therapy (0.41 ± 0.25 gm/dl, P <0.05).

Conclusion: Alternate day single tablet dosing schedule of oral iron therapy (60mg of elemental iron, ferrous sulfate) was more effective and better tolerated (gastrointestinal side effects) compared to daily supplementation in IDA.
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May 2020

Acute Effect of a Protein Supplement on Targeted Plasma Amino Acid Profile among Healthy Asian Indians: A Randomized Controlled Trial.

J Nutr Metab 2020 27;2020:8946820. Epub 2020 May 27.

Department of Physiology, St. John's Medical College, Bengaluru, India.

Background: Indians have a poor protein intake in terms of quantity as well as quality because of their predominantly cereal-based diet. However, there is limited information on circulatory amino acid levels in healthy Indians. Herein, we evaluated the acute effect of a protein supplement on the plasma levels of essential amino acids (EAAs) in healthy Indian adults, using targeted EAA analysis.

Methods: In this double-blind, randomized, crossover study, 20 healthy Indian adults were randomized to receive the test protein supplement (treatment arm,  = 10) or placebo (control arm,  = 10) with milk, after overnight fasting. After 7 days, the participants returned for the crossover treatment. Blood samples were collected at baseline and at 60 and 120 min after protein/placebo consumption. Plasma EAA levels were estimated using liquid chromatography-tandem mass spectrometry. Repeated measures ANOVA was performed to assess the effect of treatment on EAA levels. values < 0.05 were considered statistically significant.

Results: At baseline, mean plasma levels did not differ significantly between the two arms for any of the EAAs. In the treatment arm, the mean levels of all EAAs increased significantly from baseline to 60 min ( < 0.01), with no significant change from 60 to 120 min. There was no significant change in amino acid levels in the control arm. The magnitude as well as percentage of increase from baseline to 60 min was significantly greater in the treatment arm than in the control arm for all EAAs.

Conclusion: Compared to placebo, protein supplement increased circulatory amino acid levels in healthy Indians. The observed increase in EAA levels and its role in conjunction with exercise in both healthy and diseased states need to be further evaluated. This is the first dataset exploring targeted EAA profiles and the effect of a protein supplement among healthy Indians. The clinical trial is registered with CTRI/2018/12/016777.
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http://dx.doi.org/10.1155/2020/8946820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285395PMC
May 2020

Amorphous nanosilica induced toxicity, inflammation and innate immune responses: A critical review.

Toxicology 2020 08 7;441:152519. Epub 2020 Jun 7.

Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Karwar, Jodhpur, Rajasthan, India. Electronic address:

Nanoparticles are promising bioengineering platforms facilitating various consumer product formulations, including packaged food, electrical, biosensor and biomedical tools. The unique surface and physicochemical properties of amorphous nanosilica supports advanced nano-biomolecular applications for various manufacturing, biotechnology, and healthcare industries including cosmetics, packaging, implants, drug delivery systems and cancer diagnostics. The increased technological and economic benefits of amorphous nanosilica, raises concerns regarding their adverse biological effects on humans. The cellular mechanisms underlying amorphous nanosilica internalization, evasion of biological barriers, inadvertent nano-bio interactions and unexpected long term exposure effects must be taken into consideration from the diverse ecosystems and human safety aspects. Recent research studies reveal cytotoxic, inflammatory and immunomodulatory effects of amorphous nanosilica particles. Our review focuses on studies demonstrating hazardous impact of amorphous nanosilica/bio-systems interface on the cellular and biochemical processes. The review further seeks to evaluate amorphous nanosilica-induced cytotoxicity, innate immune responses, inflammation and immune related dysfunctions, and discuss open research questions related to the use of amorphous nanosilica in biomedicine.
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http://dx.doi.org/10.1016/j.tox.2020.152519DOI Listing
August 2020

The Current Indian Epidemic of Dermatophytosis: A Study on Causative Agents and Sensitivity Patterns.

Indian J Dermatol 2020 Mar-Apr;65(2):118-122

Department of Microbiology, Calcutta National Medical College, Kolkata, West Bengal, India.

Background: In the recent years, the frequency, severity, clinical characteristics, treatment response, and relapse rate of dermatophytosis have dramatically changed in India. Given the surge in dermatophytosis, we had undertaken a study to isolate and identify the common species causing dermatophyte infection and to know the efficacy of the common antifungals against them.

Materials And Methods: A total of 103 new cases that were not on any treatment for the past 3 months were included. Skin scrapings were collected for direct microscopic examination and for fungal culture in Sabouraud 4% dextrose agar (SDA) with chloramphenicol and cycloheximide slant tubes, and dermatophyte test media. Fungi were identified on the basis of their macroscopic and microscopic features with the help of lactophenol cotton blue staining and urease test. Also, the drug sensitivity of the dermatophytes was tested with the common antifungals.

Results: Of the 55 cases (53.4%) that were positive for dermatophytes in the culture, 29 showed possible contamination. was the predominant organism (49 cases) with being the commonest species (26 cases), followed by (15 patients), and (8 cases). All species of were found to be most sensitive to itraconazole amongst systemic antifungals and luliconazole amongst topical antifungals.

Conclusion: This study concluded that the causative agent for the dermatophytosis was changing in India and in our subset, caused the maximum number of infections. Itraconazole and luliconazole had the highest sensitivity amongst systemic and topical antifungals, respectively. It also showed that terbinafine had comparatively less sensitivity to most organisms.
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http://dx.doi.org/10.4103/ijd.IJD_203_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059464PMC
March 2020

tDCS combined with cognitive training in a patient with chronic traumatic head injury.

Neurophysiol Clin 2020 04 5;50(2):133-134. Epub 2020 Mar 5.

Department of Pediatric and Neonatal Physiotherapy, Maharishi Markandeshwar Institute of Physiotherapy and Rehabilitation, Maharishi Markandeshwar (Deemed to be University), Mullana 133207, Ambala, Haryana, India; Department of Physiotherapy, Maharishi Markandeshwar Medical College and Hospital, Kumarhatti 173229, Solan, Himachal Pradesh, India. Electronic address:

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http://dx.doi.org/10.1016/j.neucli.2020.02.004DOI Listing
April 2020

Selective binding of Ni and Cu metal ions with naphthazarin esters isolated from Arnebia euchroma.

Biotechnol Prog 2020 07 21;36(4):e2985. Epub 2020 Mar 21.

Food and Nutraceutical Division, Natural Product Chemistry & Process Development Lab, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India.

Naphthazarin esters (C1-C4) isolated from the roots of Arnebia euchroma are found as skilled dual chemosensors for Ni and Cu among Pb , Na , K , Hg , Mg , and Ca metal ions. C1-C4 esters exhibited a red shift of 54 nm with Ni and 30 nm with Cu metal ions in absorption. There is a formation of red-shifted bands between 517 and 613 nm in the absorption spectrum of C1-C4 sensors on binding with Ni and Cu ions. The addition of Ni and Cu ions to sensors C1-C4 stimulates a remarkable color change from reddish pink to purple and light blue, respectively. These color changes can be identified with the naked eye. The significant downfield shifts of CO and OH peaks in nuclear magnetic resonance (NMR) spectrum confirm the chelation as binding mechanism. With ultraviolet-visble and NMR studies, it is found that C1-C4 esters possessed notable selectivity and sensitivity toward Ni and Cu over other metal ions.
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http://dx.doi.org/10.1002/btpr.2985DOI Listing
July 2020

Sexual Abuse in Children and Relevance of POCSO Act-A Report of Four Cases.

Indian J Dermatol 2020 Jan-Feb;65(1):74-76

Department of Dermatology, Calcutta National Medical College, Kolkata, West Bengal, India. E-mail:

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http://dx.doi.org/10.4103/ijd.IJD_673_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986118PMC
February 2020

Mammary Extranodal Rosai-Dorfman Disease With and Without Associated Axillary Lymphadenopathy: Insights for Practitioners of Breast Pathology.

Int J Surg Pathol 2020 Aug 28;28(5):541-548. Epub 2020 Jan 28.

Mayo Clinic, Rochester, MN, USA.

Rosai-Dorfman disease is a rare proliferative histiocytic disorder of lymph nodes that is descriptively known as sinus histiocytosis with massive lymphadenopathy. Extranodal involvement of the parenchyma of the breast is uncommonly reported, with fewer than 50 cases of mammary extranodal disease detailed in the English-language literature. We characterize a retrospective series of adult female patients from a single institution with Rosai-Dorfman disease of the breast and axillary lymph nodes. Because Rosai-Dorfman disease of the breast and axillary lymph nodes may clinically, radiographically, and histologically mimic breast carcinoma and other conditions, we present an illustrated review of the disease and its relevant differential diagnoses in hopes of raising awareness and allowing for accurate management of affected patients.
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http://dx.doi.org/10.1177/1066896920901770DOI Listing
August 2020