Publications by authors named "Preeti Singh"

203 Publications

Point Prevalence of Peripheral Neuropathy in Children and Adolescents with Type 1 Diabetes Mellitus.

Indian J Pediatr 2021 Jun 10. Epub 2021 Jun 10.

Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, 110001, India.

Objective: To assess the point prevalence of peripheral neuropathy (PN) in children with type 1 diabetes mellitus (T1DM) and to determine their predictors.

Methods: In this cross-sectional study, children aged 8-18 y with T1DM on insulin therapy for > 2 y and free from acute complications were enrolled. All participants were evaluated for symptoms of PN with diabetic neuropathy symptom (DNS) score and underwent a detailed neurological examination. Assessment of nerve dysfunction was done using nerve conduction studies (NCS). The disease-related factors that increase the risk of PN were determined.

Results: Fifty children (52% boys) were enrolled with mean age of 12.2 ± 2.8 y and duration of diabetes 5.1 ± 2.1 y. No subject had clinical evidence or DNS score suggestive of PN. Twenty-eight (56%) children demonstrated subclinical neuropathy on NCS. Proportion of children with pure motor, pure sensory, and mixed motor-sensory neuropathy was 40%, 2%, and 14%, respectively. The peroneal nerve was the most common motor nerve affected. Poor glycemic control (HbA1c > 9%) and longer duration of diabetes (> 5 y) were significantly associated with the risk of PN (p value < 0.05).

Conclusion: A large proportion of children with T1DM have subclinical PN. Poor glycemic control and longer duration of diabetes are risk factors for nerve dysfunction. Neurophysiological studies should be performed in these children to facilitate early detection.
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http://dx.doi.org/10.1007/s12098-021-03742-4DOI Listing
June 2021

Acute Kidney Injury in Hospitalized Children with COVID19.

J Trop Pediatr 2021 05;67(2)

Department of Paediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi 110001, India.

Background: Acute kidney injury (AKI) has been recognized as a significant risk factor for mortality among adults with severe acute respiratory syndrome coronavirus infection.

Aim: The aim of this study is to assess the prevalence and risk factors for AKI and mortality in children with coronavirus disease 2019 (COVID19) from a resource-limited setting.

Methods: Cross-sectional analysis of laboratory confirmed COVID19 children admitted from 1 March to 30 November 2020 in a tertiary care hospital in New Delhi, India was done. Clinical features and associated comorbidities of COVID19 were noted. Baseline serum creatinine (height-independent Hoste's equation) and peak serum creatinine were used for staging of AKI by the 2012 Kidney Disease Improving Global Outcomes serum creatinine criteria. Univariate analysis and Kaplan-Meier survival analysis were used to compare the overall outcome in the AKI vs. the non-AKI group.

Results: A total of 64 810 children between 1 month and 18 years visited the hospital; 3412 were tested for suspected COVID19, 295 tested positive and 105 (54% boys) were hospitalized. Twenty-four hospitalized children (22.8%) developed AKI; 8 in Stage 1 (33.3%), 7 in Stage 2 (29.2%) and 9 in Stage 3 (37.5%) respectively. Overall, three patients received KRT. Highest reported mortality was (66.6%) in AKI Stage 3. Risk factors for AKI included associated sepsis (OR 95% CI, 1.22-9.43, p < 0.01), nephrotic syndrome (OR 95% CI, 1.13-115.5, p < 0.01), vasopressor support (OR 3.59, 95% CI, 1.37-9.40, p value< 0.007), shock at presentation (OR 2.98, 95% CI, 1.16-7.60, p value 0.01) and mechanical ventilation (OR 2.64, 95% CI, 1.04-6.71, p value< 0.03). Mortality (25.71%) was higher in the AKI group (OR 95% CI, 1.14-8.35, p < 0.023) with shock (OR 45.92; 95% CI, 3.44-612.0, p value <0.004) and ventilation (OR 46.24; 95% CI, 1.6-1333.0 p value< 0.02) as significant risk factors for mortality.

Conclusion: AKI is an important modifiable risk factor for mortality in children with COVID19 in a resource-limited setting. Our study supports the strengthening of kidney replacement therapy and its timely initiation to reduce the progression of AKI and thus mortality in children.
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http://dx.doi.org/10.1093/tropej/fmab037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195178PMC
May 2021

Sex-dependent effects of genetic upregulation of activated protein C on delayed effects of acute radiation exposure in the mouse heart, small intestine, and skin.

PLoS One 2021 24;16(5):e0252142. Epub 2021 May 24.

Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America.

Accidental exposure to ionizing radiation may lead to delayed effects of acute radiation exposure (DEARE) in many organ systems. Activated protein C (APC) is a known mitigator of the acute radiation syndrome. To examine the role of APC in DEARE, we used a transgenic mouse model with 2- to 3-fold increased plasma levels of APC (high in APC, APCHi). Male and female APCHi mice and wild-type littermates were exposed to 9.5 Gy γ-rays with their hind-legs (bone marrow) shielded from radiation to allow long-term survival. At 3 and 6 months after irradiation, cardiac function was measured with ultrasonography. At 3 months, radiation increased cardiac dimensions in APCHi males, while decreases were seen in wild-type females. At this early time point, APCHi mice of both sexes were more susceptible to radiation-induced changes in systolic function compared to wild-types. At 6 months, a decrease in systolic function was mainly seen in male mice of both genotypes. At 6 months, specimens of heart, small intestine and dorsal skin were collected for tissue analysis. Female APCHi mice showed the most severe radiation-induced deposition of cardiac collagens but were protected against a radiation-induced loss of microvascular density. Both male and female APCHi mice were protected against a radiation induced upregulation of toll-like receptor 4 in the heart, but this did not translate into a clear protection against immune cell infiltration. In the small intestine, the APCHi genotype had no effect on an increase in the number of myeloperoxidase positive cells (seen mostly in females) or an increase in the expression of T-cell marker CD2 (males). Lastly, both male and female APCHi mice were protected against radiation-induced epidermal thickening and increase in 3-nitrotyrosine positive keratinocytes. In conclusion, prolonged high levels of APC in a transgenic mouse model had little effects on indicators of DEARE in the heart, small intestine and skin, with some differential effects in male compared to female mice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252142PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143413PMC
May 2021

The Role of Interleukin-27 in Atherosclerosis: A Contemporary Review.

Cardiology 2021 May 19:1-13. Epub 2021 May 19.

Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Atherosclerosis is a chronic inflammation characterized by an imbalance between inhibitors and stimulators of the inflammatory system that leads to the formation of atherosclerotic plaques in the vessel walls. Interleukin (IL)-27 is one of the recently discovered cytokines that have an immunomodulatory role in autoimmune and inflammatory diseases. However, the definite role of IL-27 in the pathogenesis of atherosclerosis remains unclear. Recent studies on cardiomyocytes and vascular endothelium have demonstrated mechanisms through which IL-27 could potentially modulate atherosclerosis. Upregulation of the IL-27 receptor was also observed in the atherosclerotic plaques. In addition, circulatory IL-27 levels were increased in patients with acute coronary syndrome and myocardial infarction. A regenerative, neovascularization, and cardioprotective role of IL-27 has also been implicated. Future studies are warranted to elucidate the biologic function and clinical significance of IL-27 in atherosclerosis.
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http://dx.doi.org/10.1159/000515359DOI Listing
May 2021

Advancement of chimeric hybrid drugs to cure malaria infection: An overview with special emphasis on endoperoxide pharmacophores.

Eur J Med Chem 2021 Jul 4;219:113408. Epub 2021 Apr 4.

Chemical Biology Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address:

Emergence and spread of Plasmodium falciparum resistant to artemisinin-based combination therapy has led to a situation of haste in the scientific and pharmaceutical communities. Sincere efforts are redirected towards finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. Extensive research yielded the concept of "Chimeric Bitherapy (CB)" which involves the linking of two molecules with individual pharmacological activity and exhibit dual mode of action into a single hybrid molecule. Current research in this field seems to endorse hybrid molecules as the next-generation antimalarial drugs and are more effective compared to the multi-component drugs because of the lower occurrence of drug-drug adverse effects. This review is an attempt to congregate complete survey on endoperoxide based hybrid antiplasmodial molecules that will give glimpse on the future directions for successful development and discovery of useful antimalarial hybrid drugs.
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http://dx.doi.org/10.1016/j.ejmech.2021.113408DOI Listing
July 2021

Disease Spectrum of Breast Cancer Susceptibility Genes.

Front Oncol 2021 20;11:663419. Epub 2021 Apr 20.

Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Background: Pathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases, which clinicians must manage for their patients. We evaluated the disease spectrum of breast cancer susceptibility genes (BCSGs) with the aim of developing a comprehensive resource of gene-disease associations for clinicians.

Methods: Twelve genes (, and ), all of which have been conclusively established as BCSGs by the Clinical Genome Resource (ClinGen) and/or the NCCN guidelines, were investigated. The potential gene-disease associations for these 12 genes were verified and evaluated based on six genetic resources (ClinGen, NCCN, OMIM, Genetics Home Reference, GeneCards, and Gene-NCBI) and an additional literature review using a semiautomated natural language processing (NLP) abstract classification procedure.

Results: Forty-two diseases were found to be associated with one or more of the 12 BCSGs for a total of 86 gene-disease associations, of which 90% (78/86) were verified by ClinGen and/or NCCN. Four gene-disease associations could not be verified by either ClinGen or NCCN but were verified by at least three of the other four genetic resources. Four gene-disease associations were verified by the NLP procedure alone.

Conclusion: This study is unique in that it systematically investigates the reported disease spectrum of BCSGs by surveying multiple genetic resources and the literature with the aim of developing a single consolidated, comprehensive resource for clinicians. This innovative approach provides a general guide for evaluating gene-disease associations for BCSGs, potentially improving the clinical management of at-risk individuals.
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http://dx.doi.org/10.3389/fonc.2021.663419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093501PMC
April 2021

Execution and viable applications of face shield "a safeguard" against viral infections of cross-protection studies: A comprehensive review.

J Mol Struct 2021 Aug 10;1238:130443. Epub 2021 Apr 10.

Bio/Polymers Research Laboratory, Department of Chemistry, Jamia Millia Islamia, New Delhi, India.

Face shield are the unmistakable plastic gatekeepers secures eyes and face, simpler to wear and a group of specialists state face shields may supplant masks as an increasingly agreeable and progressively successful obstacle to COVID-19. Face shields are useful in stopping respiratory droplets from speading from the wearer to others. The droplets, which come into contact with the shield, are quickly spread over a large area, both transversely and vertically, over the shield, but with a shrinking concentration of droplets, as opposed to face masks, which appear to slide under the nose of the wearer or, worse, collapse entirely off the shield. Hence, a face- shield can be considered as personal protective equipment (PPE), which is a first line of resistance, utilized by the clinicians and forefront health workers for protection against the infectious body fluid and aerosols. Face-shields are mainly fabricated using polycarbonate material, because of their excellent optical transparency in UVA-visible-IR spectrum and mechanical properties. The goal of this article is to provide researchers working in the same area, as well as health and industrial staff, with a detailed analysis of the usage of face shields against bioaerosols and the need for personal security. The reviews main focus on the background of the face shield, provide assistance in the selection, its design and structure, applications, advantages and disadvantages. Lastly, people's view about the usage of face shield as it becomes an essential part of human beings like an accomplice during this current pandemic situation.
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http://dx.doi.org/10.1016/j.molstruc.2021.130443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035530PMC
August 2021

Heparanase 2 (Hpa2) attenuates the growth of pancreatic carcinoma.

Matrix Biol 2021 Apr 8. Epub 2021 Apr 8.

Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel. Electronic address:

While the pro-tumorigenic properties of the ECM-degrading heparanase enzyme are well documented, the role of its close homolog, heparanase 2 (Hpa2), in cancer is largely unknown. We examined the role of Hpa2 in pancreatic cancer, a malignancy characterized by a dense fibrotic ECM associated with poor response to treatment and bad prognosis. We show that pancreatic ductal adenocarcinoma (PDAC) patients that exhibit high levels of Hpa2 survive longer than patients with low levels of Hpa2. Strikingly, overexpression of Hpa2 in pancreatic carcinoma cells resulted in a most prominent decrease in the growth of tumors implanted orthotopically and intraperitoneally, whereas Hpa2 silencing resulted in bigger tumors. We further found that Hpa2 enhances endoplasmic reticulum (ER) stress response and renders cells more sensitive to external stress, associating with increased apoptosis. Interestingly, we observed that ER stress induces the expression of Hpa2, thus establishing a feedback loop by which Hpa2 enhances ER stress that, in turn, induces Hpa2 expression. This leads to increased apoptosis and attenuated tumor growth. Altogether, Hpa2 emerges as a powerful tumor suppressor in pancreatic cancer.
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http://dx.doi.org/10.1016/j.matbio.2021.03.002DOI Listing
April 2021

Pubertal Development and its Determinants in Adolescents With Transfusion-Dependent Thalassemia.

Indian Pediatr 2021 Mar 26. Epub 2021 Mar 26.

Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India. Correspondence to: Dr Anju Seth, Director Professor, Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi 110 001, India.

Objectives: To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT).

Methods: In this cross-sectional study from a tertiary teaching hospital in Delhi, records of adolescents aged 17-19 years with TDT on regular transfusion at thalassemia day-care centre were reviewed. Pubertal development and its determinants were assessed.

Results: Records of 58 (33 male) adolescents with TDT were reviewed. Among them, 42 (72.4%) had normal/delayed onset with spontaneous progression of puberty, while 16 (27.6%) had pubertal arrest/failure and received hormonal replacement therapy (HRT). Short stature was observed in all adolescents on HRT. Amongst other endocrinopathies, only hypoparathyroidism was found to be significantly higher in the HRT group. On multivariate analysis, serum ferritin (OR-1.005, 95% CI 1.002, 1.009) was observed to be the only significant determinant of pubertal arrest/failure.

Conclusions: A significant proportion of adolescents with TDT continue to have pubertal arrest/failure. High systemic iron load is the key determinant for this.
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March 2021

Disease spectrum of gastric cancer susceptibility genes.

Med Oncol 2021 Mar 24;38(5):46. Epub 2021 Mar 24.

Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Yawkey 7, Boston, MA, 02114, USA.

Pathogenic variants in germline cancer susceptibility genes can increase the risk of a large number of diseases. Our study aims to assess the disease spectrum of gastric cancer susceptibility genes and to develop a comprehensive resource of gene-disease associations for clinicians. Twenty-seven potential germline gastric cancer susceptibility genes were identified from three review articles and from six commonly used genetic information resources. The diseases associated with each gene were evaluated via a semi-structured review of six genetic resources and an additional literature review using a natural language processing (NLP)-based procedure. Out of 27 candidate genes, 13 were identified as gastric cancer susceptibility genes (APC, ATM, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH-Biallelic, PALB2, SMAD4, and STK11). A total of 145 gene-disease associations (with 45 unique diseases) were found to be associated with these 13 genes. Other gastrointestinal cancers were prominent among identified associations, with 11 of 13 gastric cancer susceptibility genes also associated with colorectal cancer, eight genes associated with pancreatic cancer, and seven genes associated with small intestine cancer. Gastric cancer susceptibility genes are frequently associated with other diseases as well as gastric cancer, with potential implications for how carriers of these genes are screened and managed. Unfortunately, commonly used genetic resources provide heterogeneous information with regard to these genes and their associated diseases, highlighting the importance of developing guides for clinicians that integrate data across available resources and the medical literature.
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http://dx.doi.org/10.1007/s12032-021-01495-wDOI Listing
March 2021

Levels of lead, aluminum, and zinc in occupationally exposed workers of North-Western India.

J Basic Clin Physiol Pharmacol 2021 Mar 12. Epub 2021 Mar 12.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Objectives: Metals including lead (Pb), aluminum (Al), and zinc (Zn) are widely used in factories such as welding, handicrafts, and paint. Occupational exposure to such metals causes a wide range of biological effects, depending upon the metal levels and duration of exposure. Accumulation of these metals may lead to several adverse health effects such as neurodegenerative diseases and cancer. The study aimed to evaluate Pb, Al, and Zn levels in occupationally exposed workers of North-Western India and create awareness about its toxicity and adverse outcomes.

Methods: The study included 120 factory workers (exposed) and 100 healthy controls (nonexposed); age ranged 18-78 years. Blood Pb and serum Al was estimated by graphite furnace atomic absorption spectrophotometry and serum Zn was estimated by flame atomic absorption spectrophotometry (ICE 3000, Thermo Fisher Scientific).

Results: Results indicated significantly higher levels of Pb, Al, and Zn in the exposed than the nonexposed. No significant difference was observed in metal levels, based on age and duration of exposure. Painters showed higher blood Pb, whereas welders were found to have higher serum Al and Zn levels.

Conclusions: To conclude, workers showed higher levels of metals and it may cause deleterious effects on the health of workers occupationally exposed to these metals. Appropriate maintenance regarding worker's safety and hygiene is required to protect them from the harmful effects of these toxic metals.
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http://dx.doi.org/10.1515/jbcpp-2020-0220DOI Listing
March 2021

Sub-internal limiting membrane haemorrhage following pancytopenia in megaloblastic anemia.

Clin Exp Optom 2021 Mar 1:1-3. Epub 2021 Mar 1.

Department of Ophthalmology, Lady Hardinge Medical College and Associated SSKH and KSC Hospital, University of Delhi, New Delhi, India.

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http://dx.doi.org/10.1080/08164622.2021.1878842DOI Listing
March 2021

Non-medullary Thyroid Cancer Susceptibility Genes: Evidence and Disease Spectrum.

Ann Surg Oncol 2021 Mar 3. Epub 2021 Mar 3.

Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA.

Background: The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention.

Objective: The aim of this study was to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes.

Methods: Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity.

Results: Among 25 candidate genes, 10 (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions.

Conclusion: Twelve genes predisposing to NMTC and their associated disease spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.
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http://dx.doi.org/10.1245/s10434-021-09745-xDOI Listing
March 2021

Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival.

Sci Rep 2021 Feb 25;11(1):4688. Epub 2021 Feb 25.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.

Cytoskeletal structures of Apicomplexan parasites are important for parasite replication, motility, invasion to the host cell and survival. Apicortin, an Apicomplexan specific protein appears to be a crucial factor in maintaining stability of the parasite cytoskeletal assemblies. However, the function of apicortin, in terms of interaction with microtubules still remains elusive. Herein, we have attempted to elucidate the function of Plasmodium falciparum apicortin by monitoring its interaction with two main components of parasite microtubular structure, α-tubulin-I and β-tubulin through in silico and in vitro studies. Further, a p25 domain binding generic drug Tamoxifen (TMX), was used to disrupt PfApicortin-tubulin interactions which led to the inhibition in growth and progression of blood stage life cycle of P. falciparum.
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http://dx.doi.org/10.1038/s41598-021-83513-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907060PMC
February 2021

Association of microRNA expression with changes in immune markers in workers with cadmium exposure.

Chemosphere 2021 Jul 26;274:129615. Epub 2021 Jan 26.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India. Electronic address:

Human exposure to cadmium (Cd) is known to produce severe health effects. Recently, molecular mechanism of Cd toxicity has revealed the role of Cd in causing epigenetic alterations. miRNAs are small, non-coding RNAs which are involved in translational repression of genes. Therefore, the aim of the present study was to evaluate the alterations in expression of miRNAs associated with inflammation, carcinogenesis and, further, study their possible correlation with immune profile, in occupationally Cd exposed workers of Jodhpur. 106 workers from metal handicraft and welding factories were recruited as subjects, while, 80 apparently healthy non-exposed individuals served as control for this study. Blood Cd levels (BCd) were determined by Graphite Furnace Atomic Absorption Spectroscopy (GFAAS). Lymphocyte cell subset were measured by flow cytometry, serum interleukins were assessed by ELISA and miRNA expression was determined by Real Time Polymerase Chain Reaction (RT-PCR). BCd levels were significantly higher in the exposed individuals when compared to the non-exposed, with welders reporting the highest amongst all. Among the lymphocyte subset, exposed group showed significantly higher percentage of Th17 and lower percentage of Treg population. Cytokine profile expressed by exposed workers were predominantly pro-inflammatory in nature. Among, the studied miRNAs, miR-221 was significantly higher in exposed group with a fold change of 3.05. Additionally, miR-221 and miR-155 showed significant positive correlation with Th17 cell %. Regression analysis showed duration of exposure and IL-17 to have significant effect on miR-221 in exposed group. In conclusion, miR-221 was significantly upregulated in exposed and was correlated with immune alteration making it a potential candidate for further exploration of mechanism underlying Cd toxicity.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129615DOI Listing
July 2021

Assessement of Blood Lead and Cadmium Levels in Occupationally Exposed Workers of Jodhpur, Rajasthan.

Indian J Clin Biochem 2021 Jan 14;36(1):100-107. Epub 2020 Mar 14.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.

In spite of the established knowledge regarding their toxicities, occupational exposure to heavy metals like lead and cadmium still continues because of their wide distribution in environment. Due to lack of awareness, most of the workers usually eat, smoke, drink at their workplace which may aggravate the metal exposure. The present study was planned to assess the blood levels of lead and cadmium in occupationally exposed workers of Jodhpur (India). A total of 110 individuals working in different industrial set ups (furniture, metal handicraft, welders) of Jodhpur district (exposed group), aged between 20 and 60 years and 97 apparently healthy people (controls) with no history of occupational heavy metal exposure aged between 25 and 60 were recruited. Details of personal habits and demographics were recorded by means of self-developed questionnaire. 5 ml of whole blood was drawn from every individual. Metal levels were measured by graphite furnace atomic absorption spectrophotometer. Statistical analysis was done using GraphPad Prism Software. Results showed that Blood Lead Level and Blood Cadmium Level (CdB) were significantly higher in the exposed group as compared to the non-exposed group. Significant age and gender-based differences were found in terms of blood cadmium levels but no such difference was observed in case of blood lead. The study also revealed that higher blood levels of these metals in workers are influenced by their occupational practices, lack of protection against workplace environment pollutants, thus increasing their susceptibility to metal toxicity.
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http://dx.doi.org/10.1007/s12291-020-00878-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817726PMC
January 2021

Pathogen induced subversion of NAD metabolism mediating host cell death: a target for development of chemotherapeutics.

Cell Death Discov 2021 Jan 13;7(1):10. Epub 2021 Jan 13.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India.

Hijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics.
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http://dx.doi.org/10.1038/s41420-020-00366-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806871PMC
January 2021

Pemphigoid Gestationis-A Rare Pregnancy Dermatoses.

J Obstet Gynaecol India 2020 Dec 12;70(6):527-528. Epub 2020 Jan 12.

Department of Pathology, Dr. Ram Manohar Lohia Hospital and Post Graduate Institute of Medical Education and Research, Baba Kharak Singh Marg, New Delhi, 110001 India.

Pemphigoid gestationis is a rare subepidermal bullous dermatosis of pregnancy, caused by the interaction of IgG1 auto-antibodies with 180 kD BP Antigen 2. This disease can lead to preterm delivery, but the neonate is affected in only 10% cases. The treatment of choice in pemphigoid gestationis is systemic corticosteroids.
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http://dx.doi.org/10.1007/s13224-019-01302-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758377PMC
December 2020

Brief cognitive behavior group therapy for social anxiety among medical students: A randomized placebo-controlled trial.

Asian J Psychiatr 2021 Jan 15;55:102526. Epub 2020 Dec 15.

Consultant Behavioural Medicine Unit, Department of Clinical Psychology, M.V.Govindaswamy Building, NIMHANS, Bengaluru, 560029, India. Electronic address:

Objective: To compare brief cognitive behavior group therapy (bCBGT) for social anxiety disorder (SAD) to a credible placebo, psychoeducational-supportive therapy (PST), in a sample of medical students.

Method: This was a single-center, rater-blind, randomized, attention placebo-controlled, parallel-group study. Participants were 50 consenting undergraduate medical students of a state government medical college in Cuttack, India having a primary diagnosis of SAD, who recieved 6 weekly 2-h group sessions. Assessments were carried out at baseline, post intervention and at two-month follow. Independent raters assessed the participants on the Liebowitz Social Anxiety Scale and Clinical Global Impression- Improvement scale (CGI-I). Social Phobia Inventory (SPIN), a self-rated measure, was administered in the same periods.

Results: bCBGT group improved significantly across periods from pre-treatment to post-treatment and from pre-treatment to two-month follow-up. bCBGT was statistically superior to PST at the post-treatment and follow-up assessments and showed large effect sizes at both post-treatment and follow-up.

Conclusions: A 6-session bCBGT is an efficacious treatment for SAD among medical students. A longer follow-up and replication in other groups, and clinical settings are necessary for generalization to a broader SAD population.
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http://dx.doi.org/10.1016/j.ajp.2020.102526DOI Listing
January 2021

Burden of increasing opioid use in the treatment of migraine: Results from the Migraine in America Symptoms and Treatment Study.

Headache 2021 Jan 16;61(1):103-116. Epub 2020 Dec 16.

Department of Clinical Research, Vedanta Research, Chapel Hill, NC, USA.

Objective: We sought to assess factors associated with the frequency of self-reported prescription opioid use in persons with migraine, including demographic variables, comorbidities, headache characteristics, and patterns of consultation.

Background: Despite the dose-dependent effect of opioids on migraine progression and the association with negative outcomes, migraine treatment often includes opioids. The Migraine in America Symptoms and Treatment Study focuses on individuals with migraine who receive prescription acute medications, including those receiving and those not receiving opioids.

Methods: This web-based panel survey identified people in the United States with migraine using a validated screener. This analysis stratified people with migraine into 4 groups based on days of monthly opioid use: non-opioid users, ≤3 days, 4-9 days, and ≥10 days per month.

Results: Of 15,133 respondents with migraine, 4701 (31%) reported acute prescription medication use for headache/migraine in the previous 3 months (mean age 45 years, 71.6% [3367/4701] female), of whom 32.5% (1528/4701) reported opioid use. About one-third of respondents with primary care or neurology consults in the prior 6 months reported receiving an opioid, and more than half of respondents (209/391, 53.5%) with a pain clinic consultation did so. Models compared those using opioids ≤3 days/month (879/4701, 18.7%), 4-9 days/month (304/4701, 6.5%), ≥10 days/month (345/4701, 7.3%) to non-opioid users (3173/4701, 67.5%). Compared to non-opioid users, infrequent users (≤3 days/month) were more likely to be male and less likely to have chronic migraine or to screen positive for anxiety and depression; and frequent opioid users (the 4-9 days/month and the ≥10 days/month groups) were more likely to be male, to smoke, to be obese, to report greater pain interference, to have moderate to severe disability, to have symptoms of anxiety and depression, to use fewer triptans and nonsteroidal anti-inflammatory drugs, and to have poor acute treatment optimization.

Conclusion: Among prescription medication users, this cross-sectional analysis shows that increasing use of prescription opioids is associated with male gender, chronic migraine, more severe disability, anxiety and depression, poor acute treatment optimization, and treatment in a pain clinic.
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http://dx.doi.org/10.1111/head.14018DOI Listing
January 2021

Molecular investigation of three leopards death: A case of suspicious revenge killing.

Forensic Sci Int Genet 2021 Mar 12;51:102425. Epub 2020 Nov 12.

Wildlife Institute of India, Dehra Dun, India.

We report a case study wherein we established the putative cause of the death of three leopards by identifying the species and number of individual prey species from the gut contents using molecular tools. In a National Park within Northern part of India, the suspicious death of three leopards (Panthera pardus) was reported from different localities on the same day. The gut contents from the three leopard carcasses were collected during postmortem and sent to us to confirm the prey species. We used mitochondrial DNA cytochrome b (Cyt b) and control region (CR), and nuclear microsatellites for molecular identification of species and individual identification, respectively, from the gut contents. Mitochondrial sequences confirmed that the undigested remnants collected from the gut contents were of the domestic dog (Canis lupus familiaris). Furthermore, the microsatellite analysis of the gut contents highlighted the consumption of the same dog by all the three deceased leopards. Since the National Park was one of the major human-wildlife interaction zones, consuming the same dog by the leopards implies suspicious poisoning for revenge. The use of dog carcass for the possible poisoning for the mass-scale killing of the protected species is a severe wildlife offense.
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http://dx.doi.org/10.1016/j.fsigen.2020.102425DOI Listing
March 2021

Estimation of lymphocyte subsets and cytokine levels in workers occupationally exposed to cadmium.

J Trace Elem Med Biol 2021 Mar 12;64:126681. Epub 2020 Nov 12.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India. Electronic address:

Introduction: Occupational exposure to Cadmium (Cd) may have serious health effect on workers. However, little is known about its effect on immune system. Moreover, previous studies have been inconclusive in stating the effect of Cd on immune system. The aim of our study was to estimate immune parameters in workers occupationally exposed to Cd.

Material And Methods: 110 individuals occupationally exposed to Cd and 97 apparently healthy non-exposed individuals were recruited for this study. Blood Cadmium levels were determined by AAS. Lymphocyte subset were analyzed using flow cytometry and the cytokine levels were determined by ELISA.

Results: Exposed group have significantly higher levels of B-Cd. % of CD8 cells were higher in exposed while % of CD4 cells showed a decreasing trend in the exposed group. Among the CD3CD4 T cell subsets Th1 (%) and Tregs (%) cells were lower while Th17 (%) were higher in exposed group. Increased levels of IL-4 (Th2), IL-6 (Th2) and TNF- α (Th1) and decreased levels of IL-2 (Th1) and IL-10 (Tregs) were observed in Cd exposed workers which is indicative of a predominant pro-inflammatory response in Cd exposed workers. IL-17 (Th17) levels did not show any significant difference between the two groups. Increased Th17/Tregs ratio in the exposed group is also suggestive of an increased pro-inflammatory immune response in exposed group.

Conclusion: To conclude, even low level of exposure to Cd in occupational settings is associated with alterations in Th17 cells, which may further predispose an individual to other systemic abnormalities.
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http://dx.doi.org/10.1016/j.jtemb.2020.126681DOI Listing
March 2021

Metastatic subretinal abscess in a patient with perinephric abscess.

Indian J Ophthalmol 2020 Nov;68(11):2580-2582

Department of Ophthalmology, Lady Hardinge Medical College and Associated Hospitals, University of Delhi, New Delhi, India.

An 80-year-old lady with uncontrolled type 2 diabetes developed fever and abdominal pain followed by a sudden diminution of vision in her left eye. Right infra-renal abscess accounted for abdominal pain. A metastatic left subretinal abscess was diagnosed subsequently. Medical management for her systemic condition initiated. Vitreous biopsy was performed along-with intravitreal antibiotic administration. Because of no clinical recovery, patient underwent pars plana vitrectomy. Prompt systemic stabilization and a timely surgical intervention in the left eye resulted in a satisfactory visual gain. Metastatic subretinal abscess following a perinephric abscess is rare phenomenon and only a few cases are reported to date.
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http://dx.doi.org/10.4103/ijo.IJO_1369_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774150PMC
November 2020

CHAOS: A fetal autopsy report.

J Family Med Prim Care 2020 Aug 25;9(8):4448-4450. Epub 2020 Aug 25.

Department of Obstetrics & Gynecology, AIIMS, Rishikesh, Uttarakhand, India.

Congenital high airway obstruction syndrome (CHAOS) is a rare congenital malformation, which results from deficient recanalization of the upper airways. Laryngeal atresia is the most common cause, other etiologies being trachea atresia, laryngeal or tracheal webs, subglottic stenosis, obstructing laryngeal cysts, and laryngeal or tracheal agenesis. There is decreased clearance of the fluid produced by fetal lungs due to obstruction leading to increased intratracheal pressure and thereby secondary proliferative lung growth. The heart becomes compressed in the midline due to hyperexpansion of the lungs causing elevated intrathoracic pressure, decreased venous return, and fetal cardiac failure. This sequence causes ascites, placento-megaly, and eventually hydrops fetalis. We present a case of antenatal diagnosis of a fetus with CHAOS corroborated by fetal autopsy.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_792_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586612PMC
August 2020

Evaluation of oxidative stress and pro-inflammatory cytokines in occupationally cadmium exposed workers.

Work 2021 ;69(1):67-73

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.

Background: Cadmium (Cd) exposure in environmental and occupational settings is a major public health concern. Cd exposure is associated with the production of free radicle and reactive oxygen species. The aim of the present study is to evaluate the effect of occupational exposure to Cd on oxidative stress and pro-inflammatory biomarkers in the workers.

Methods: 100 occupationally exposed individuals working in the metal handicraft industry and welding industry were recruited from the industrial area of Jodhpur, Rajasthan. Blood Cd levels were estimated using atomic absorption spectroscopy. Serum Total Antioxidant Capacity (TAC), Catalase (CAT), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) levels were measured by colorimetric method to assess oxidative status and serum IL-6 and TNF-α were measured by ELISA to assess inflammatory status.

Results: The median Cd levels in the study population was 2.40μg/L, with welders having significantly higher Cd levels than metal handicraft workers. Among the oxidative stress markers, TAC and CAT were significantly lower, while MDA was significantly higher in subjects with high Cd levels. The Cd levels showed a significant negative and positive correlation with TAC and MDA, respectively. IL- 6 and TNF-α did not show a significant difference between the study groups, but both had an inverse correlation with antioxidant enzymes.

Conclusion: Occupational exposure to even low levels of Cd may result in oxidative stress in workers primarily via decrease in antioxidant enzymes and increasing lipid peroxidation. Increased oxidative stress in turn may result in immune cell activation which may result in increased concentration of pro-inflammatory cytokine in the exposed workers.
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http://dx.doi.org/10.3233/WOR-203302DOI Listing
January 2021

Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling.

Aging Cell 2020 11 17;19(11):e13261. Epub 2020 Oct 17.

Division of Hematology & Oncology, Department of Internal Medicine, Texas Tech University Medical Sciences Center, Lubbock, TX, USA.

Age-associated mitochondrial dysfunction and oxidative damage are primary causes for multiple health problems including sarcopenia and cardiovascular disease (CVD). Though the role of Nrf2, a transcription factor that regulates cytoprotective gene expression, in myopathy remains poorly defined, it has shown beneficial properties in both sarcopenia and CVD. Sulforaphane (SFN), a natural compound Nrf2-related activator of cytoprotective genes, provides protection in several disease states including CVD and is in various stages of clinical trials, from cancer prevention to reducing insulin resistance. This study aimed to determine whether SFN may prevent age-related loss of function in the heart and skeletal muscle. Cohorts of 2-month-old and 21- to 22-month-old mice were administered regular rodent diet or diet supplemented with SFN for 12 weeks. At the completion of the study, skeletal muscle and heart function, mitochondrial function, and Nrf2 activity were measured. Our studies revealed a significant drop in Nrf2 activity and mitochondrial functions, together with a loss of skeletal muscle and cardiac function in the old control mice compared to the younger age group. In the old mice, SFN restored Nrf2 activity, mitochondrial function, cardiac function, exercise capacity, glucose tolerance, and activation/differentiation of skeletal muscle satellite cells. Our results suggest that the age-associated decline in Nrf2 signaling activity and the associated mitochondrial dysfunction might be implicated in the development of age-related disease processes. Therefore, the restoration of Nrf2 activity and endogenous cytoprotective mechanisms by SFN may be a safe and effective strategy to protect against muscle and heart dysfunction due to aging.
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http://dx.doi.org/10.1111/acel.13261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681049PMC
November 2020

Assessment of circulating miR-20b, miR-221, and miR-155 in occupationally lead-exposed workers of North-Western India.

Environ Sci Pollut Res Int 2021 Jan 9;28(3):3172-3181. Epub 2020 Sep 9.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Lead (Pb), a toxic heavy metal, is capable of inducing several adverse health effects following its accumulation in the body. Lead is a potential carcinogen, capable of causing multisystem alterations. Recent reports identify small regulatory RNA molecules-miRNAs-which show differential expression in individuals exposed to similar levels of lead. These miRNAs can become potential molecular biomarkers of lead toxicity in the future and may unravel the possible molecular pathways through which this metal may exert its toxic manifestations. The present study aimed to assess the circulating levels of miRNA-20b, 221, and 155 in occupationally lead-exposed workers and correlate them with blood lead levels. One hundred ten participants working in various factories of Jodhpur and 97 participants not occupationally exposed to lead were recruited after obtaining due informed consent. Blood lead level (BLL) was estimated by graphite furnace atomic absorption spectrophotometry (GF-AAS). Circulating miRNAs were isolated from serum by Qiagen miRNA isolation kit and converted to cDNA by commercial kit. Expression profiles of miR-20b, miR-221, and miR-155 were performed in RT-PCR using Qiagen miRNA PCR assays. The blood lead level (mean ± SD) of occupationally lead-exposed subjects was 6.94 ± 11.96 μg/dL while that of non-exposed was 2.39 ± 4.66 μg/dL. Out of the three miRNAs, miR-155 and miR-221 were significantly upregulated, while miR-20b did not show significant difference among study groups. The fold change of miR-20b, miR-221 and miR-155 expression were 1.08, 2.71 and 2.07 respectively. Functional analysis revealed that these miRNAs have the potential to trigger various genes and cellular pathways. The findings of our study highlight the importance of miRNA dysregulation in lead-exposed individuals that may contribute to the systemic effects of lead toxicity.
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http://dx.doi.org/10.1007/s11356-020-10676-5DOI Listing
January 2021

Effect of metallothionein 1A rs8052394 polymorphism on lead, cadmium, zinc, and aluminum levels in factory workers.

Toxicol Ind Health 2020 Oct 20;36(10):816-822. Epub 2020 Aug 20.

Department of Biochemistry, 410730All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Metallothioneins (MTs) are low molecular weight cysteine-rich, metal-binding proteins. They are involved in transportation and detoxification of heavy metals, homeostasis of essential metals, and as antioxidation against reactive oxygen species. Polymorphisms in a gene may increase or decrease the expression efficiency of a gene. This study aimed to determine the genetic effect of MT1A rs8052394 on lead (Pb), cadmium (Cd), zinc (Zn), and aluminum (Al) levels in factory workers. The study included 100 occupationally heavy metal exposed workers from different factories around Jodhpur. Pb, Cd, Zn, and Al levels were measured by atomic absorption spectrophotometry. Individuals with the GG genotype had lower Pb, Zn, and Al levels and higher Cd levels than AA and AG genotypes. The genotyping of MT1A rs8052394 was done by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). The mean ± standard deviation of Pb, Cd, Zn, and Al was 5.88 ± 13.28 µg/dL, 3.52 ± 1.25 µg/L, 16.45 ± 16.69 µg/dL, and 58.92 ± 58.91 µg/L, respectively. A significant association was found between single-nucleotide polymorphisms (SNPs) of MT1A gene and Cd ( = 0.006) and with Zn levels ( = 0.031) but no association found with Pb and Al levels. Among the study population, 78 participants were homozygote major (AA), 19 were heterozygote (AG), and 3 were homozygote minor (GG). The test presented the genotypic distribution of all three genotypes under the Hardy-Weinberg equilibrium ( > 0.05). The frequency of the A allele was 87.5% (175) and the G allele was 12.5% (25). To conclude, polymorphism in rs8052394 of the MT1A gene is associated with increased metal accumulation which in turn may lead to increased toxic effects in the exposed individuals. Factory workers thus, should be more cautious about protecting their health against the toxic effects of heavy metals.
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http://dx.doi.org/10.1177/0748233720947518DOI Listing
October 2020

Blood lead and cadmium levels in occupationally exposed workers and their effect on markers of DNA damage and repair.

Environ Geochem Health 2021 Jan 19;43(1):185-193. Epub 2020 Aug 19.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Occupational exposure to heavy metals like lead and cadmium causes a wide range of biological effects and may elevate the risk of genetic damage. Heavy metal toxicity is now becoming a significant public health problem. There are many discrepancies in the results of the studies on the genotoxicity of heavy metals. Therefore, the study aimed to estimate lead, cadmium, and 8-OHdG levels (8-hydroxy-2-deoxyguanosine) and expression of DNA repair gene OGG1 (8-oxoguanine DNA glycosylase 1) in occupationally heavy metal exposed workers. The study comprised 100 workers, occupationally exposed to lead and cadmium from different factories and 100 controls without history of metal exposure. The lead and cadmium mean ± SD were 5.69 ± 12.07 µg/dL and 3.44 ± 1.33 µg/L in the cases and 1.27 ± 1.10 µg/dL and 1.07 ± 0.67 µg/L in the controls. The 8-OHdG concentration was significantly higher in the cases than the controls. Cadmium showed a significant positive correlation with 8-OHdG in the cases. The expression of OGG1 was significantly down-regulated in the cases compared to the controls. Lead levels did not show any significant correlation with OGG1, whereas cadmium level had a significant positive correlation with OGG1 in the cases. To conclude, the exposure to heavy metals is associated with increased oxidative DNA damage and impaired expression of the DNA repair gene, OGG1.
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http://dx.doi.org/10.1007/s10653-020-00696-yDOI Listing
January 2021