1.Sarcopenia is common in ulcerative colitis and correlates with disease activity
Pardhu B NEELAM ; Rimesh PAL ; Pankaj GUPTA ; Anupam K SINGH ; Jimil SHAH ; Harshal S MANDAVDHARE ; Harjeet SINGH ; Aravind SEKAR ; Sanjay K BHADADA ; Usha DUTTA ; Vishal SHARMA
Intestinal Research 2024;22(2):162-171
		                        		
		                        			 Background/Aims:
		                        			Association of sarcopenia with disease severity in ulcerative colitis (UC) is not clearly defined. We planned to estimate the prevalence of sarcopenia in patients with UC as per the revised definition and its relation with the disease severity. 
		                        		
		                        			Methods:
		                        			A cross-sectional assessment of sarcopenia in patients with UC was performed. Disease activity was graded according to complete Mayo score. Hand grip strength was assessed with Jamar hand dynamometer, muscle mass using a dual energy X-ray absorptiometry scan, and physical performance with 4-m walk test. Sarcopenia was defined as a reduction of both muscle mass and strength. Severe sarcopenia was defined as reduced gait speed in presence of sarcopenia. 
		                        		
		                        			Results:
		                        			Of 114 patients (62 males, mean age: 36.49±12.41 years), 32 (28%) were in remission, 46 (40.4%) had mild-moderate activity, and 36 (31.6%) had severe UC. Forty-three patients (37.7%) had probable sarcopenia, 25 (21.9%) had sarcopenia, and 14 (12.2%) had severe sarcopenia. Prevalence of sarcopenia was higher in active disease (2 in remission, 6 in active, and 17 in severe, P<0.001). Of 14 with severe sarcopenia, 13 had severe UC while 1 had moderate UC. On multivariate analysis, lower body mass index and higher Mayo score were associated with sarcopenia. Of 37 patients with acute severe colitis, 16 had sarcopenia. Requirement of second-line therapy was similar between patients with and without sarcopenia. On follow-up (median: 18 months), there was a non-significant higher rate of major adverse events in those with sarcopenia (47.4% vs. 33.8%, P=0.273). 
		                        		
		                        			Conclusions
		                        			Sarcopenia and severe sarcopenia in UC correlate with the disease activity. 
		                        		
		                        		
		                        		
		                        	
2.Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing
Niraj KUMARI ; Rajneesh K. SINGH ; Shravan K. MISHRA ; Narendra KRISHNANI ; Samir MOHINDRA ; Raghvendra L.
Journal of Pathology and Translational Medicine 2021;55(3):192-201
		                        		
		                        			Background:
		                        			The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. 
		                        		
		                        			Methods:
		                        			We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. 
		                        		
		                        			Results:
		                        			There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2–257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1–31/case), while PB showed variations in 51 genes (1–29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). 
		                        		
		                        			Conclusions
		                        			The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.
		                        		
		                        		
		                        		
		                        	
3.The prevalence of sarcopenic obesity in community-dwelling healthy Indian adults - The Sarcopenic Obesity-Chandigarh Urban Bone Epidemiological Study (SO-CUBES)
Rimesh PAL ; Sanjay K. BHADADA ; Anshita AGGARWAL ; Tulika SINGH
Osteoporosis and Sarcopenia 2021;7(1):24-29
		                        		
		                        			Objectives:
		                        			To determine the prevalence of sarcopenia obesity (SO) in healthy Indian adults and delineate the relative impact of the 3 indices of obesity [body mass index (BMI), waist circumference (WC), fat mass percent (FM%)] with regards to inter-definitional agreement and their relationship with usual gait speed (GS). 
		                        		
		                        			Methods:
		                        			Apparently healthy adults (aged ≥ 20 years) with no background history of comorbidities were enrolled from the community by door-to-door survey. Following blood investigations, individuals with biochemical abnormalities were excluded. Enrolled participants underwent dual-energy X-ray absorptiometry (DXA). Sarcopenia was defined according to EWGSOP2 consensus based on indigenous cut-offs obtained from the Sarcopenia-Chandigarh Urban Bone Epidemiological Study (Sarco-CUBES). Obesity was defined based on BMI (≥ 25.0 kg/m2) or WC (> 90 cm in men, > 80 cm in women) or DXA-derived FM% (> 32% in men, > 40% in women). 
		                        		
		                        			Results:
		                        			Data of 804 participants were analyzed after exclusion. The mean ± SD for BMI, WC, and FM% were 26.5 ± 2.7 kg/m2, 86.8 ± 9.6, and 34.7 ± 7.3%, respectively. Prevalence of sarcopenia was 3.2%. Based on BMI, WC, and FM%, the prevalence of SO in elderly subjects (≥65 years) was 5.4%, 5.4%, and 6.3%, respectively. Using Cohen’s kappa, inter-definitional agreement between the 3 groups was ‘almost perfect’. FM%, and not BMI/WC, emerged as a significant predictor of GS on multiple linear regression analysis. 
		                        		
		                        			Conclusions
		                        			The prevalence of SO in healthy elderly Indian adults is 5.4%–6.3%. Either BMI/WC/FM% can be used to correctly identify individuals with SO.
		                        		
		                        		
		                        		
		                        	
4.The prevalence of sarcopenic obesity in community-dwelling healthy Indian adults - The Sarcopenic Obesity-Chandigarh Urban Bone Epidemiological Study (SO-CUBES)
Rimesh PAL ; Sanjay K. BHADADA ; Anshita AGGARWAL ; Tulika SINGH
Osteoporosis and Sarcopenia 2021;7(1):24-29
		                        		
		                        			Objectives:
		                        			To determine the prevalence of sarcopenia obesity (SO) in healthy Indian adults and delineate the relative impact of the 3 indices of obesity [body mass index (BMI), waist circumference (WC), fat mass percent (FM%)] with regards to inter-definitional agreement and their relationship with usual gait speed (GS). 
		                        		
		                        			Methods:
		                        			Apparently healthy adults (aged ≥ 20 years) with no background history of comorbidities were enrolled from the community by door-to-door survey. Following blood investigations, individuals with biochemical abnormalities were excluded. Enrolled participants underwent dual-energy X-ray absorptiometry (DXA). Sarcopenia was defined according to EWGSOP2 consensus based on indigenous cut-offs obtained from the Sarcopenia-Chandigarh Urban Bone Epidemiological Study (Sarco-CUBES). Obesity was defined based on BMI (≥ 25.0 kg/m2) or WC (> 90 cm in men, > 80 cm in women) or DXA-derived FM% (> 32% in men, > 40% in women). 
		                        		
		                        			Results:
		                        			Data of 804 participants were analyzed after exclusion. The mean ± SD for BMI, WC, and FM% were 26.5 ± 2.7 kg/m2, 86.8 ± 9.6, and 34.7 ± 7.3%, respectively. Prevalence of sarcopenia was 3.2%. Based on BMI, WC, and FM%, the prevalence of SO in elderly subjects (≥65 years) was 5.4%, 5.4%, and 6.3%, respectively. Using Cohen’s kappa, inter-definitional agreement between the 3 groups was ‘almost perfect’. FM%, and not BMI/WC, emerged as a significant predictor of GS on multiple linear regression analysis. 
		                        		
		                        			Conclusions
		                        			The prevalence of SO in healthy elderly Indian adults is 5.4%–6.3%. Either BMI/WC/FM% can be used to correctly identify individuals with SO.
		                        		
		                        		
		                        		
		                        	
5.Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing
Niraj KUMARI ; Rajneesh K. SINGH ; Shravan K. MISHRA ; Narendra KRISHNANI ; Samir MOHINDRA ; Raghvendra L.
Journal of Pathology and Translational Medicine 2021;55(3):192-201
		                        		
		                        			Background:
		                        			The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. 
		                        		
		                        			Methods:
		                        			We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. 
		                        		
		                        			Results:
		                        			There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2–257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1–31/case), while PB showed variations in 51 genes (1–29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). 
		                        		
		                        			Conclusions
		                        			The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.
		                        		
		                        		
		                        		
		                        	
6.Erratum to: Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT
N. T K THANSEER ; Sanjay Kumar BHADADA ; Ashwani SOOD ; Ashwin Singh PARIHAR ; Divya DAHIYA ; Priyanka SINGH ; Rajender Kumar BASHER ; Ashim DAS ; Bhagwant R MITTAL
Nuclear Medicine and Molecular Imaging 2018;52(1):85-85
		                        		
		                        			
		                        			Owing to an oversight in manuscript preparation, the name of the fifth author was rendered incorrectly. The correct spelling is Divya Dahiya.
		                        		
		                        		
		                        		
		                        	
7.Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT
N T K THANSEER ; Sanjay Kumar BHADADA ; Ashwani SOOD ; Ashwin Singh PARIHAR ; Divya DAHIYA ; Priyanka SINGH ; Rajender Kumar BASHER ; Ashim DAS ; Bhagwant R MITTAL
Nuclear Medicine and Molecular Imaging 2018;52(2):154-158
		                        		
		                        			
		                        			 ¹â¸F-Fluorocholine (FCH) PET/CT is evolving as a functional imaging modality for the preoperative imaging of abnormal parathyroid tissue(s) helping to localize eutopic and ectopic parathyroid tissue and limit the extent of surgery. FCH PET/CT may show incidental uptake in various thyroid lesions necessitating further evaluation, whereas the role of ¹â¸F-fluorodeoxyglucose (FDG) PET/CT in the detection of incidental thyroid nodules is well documented. The case of a middle-aged woman with dual pathology of parathyroid adenoma and papillary thyroid cancer detected on FCH and FDG PET/CT is presented. 
		                        		
		                        		
		                        		
		                        	
8.Erratum to: Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT
N. T K THANSEER ; Sanjay Kumar BHADADA ; Ashwani SOOD ; Ashwin Singh PARIHAR ; Divya DAHIYA ; Priyanka SINGH ; Rajender Kumar BASHER ; Ashim DAS ; Bhagwant R MITTAL
Nuclear Medicine and Molecular Imaging 2018;52(1):85-85
		                        		
		                        			
		                        			 Owing to an oversight in manuscript preparation, the name of the fifth author was rendered incorrectly. The correct spelling is Divya Dahiya. 
		                        		
		                        		
		                        		
		                        	
9.Development of a High-Resolution Multi-Locus Microsatellite Typing Method for Colletotrichum gloeosporioides.
Nikita MEHTA ; Ferry HAGEN ; Sadaf AAMIR ; Sanjay K SINGH ; Abhishek BAGHELA
Mycobiology 2017;45(4):401-408
		                        		
		                        			
		                        			Colletotrichum gloeosporioides is an economically important fungal pathogen causing substantial yield losses indifferent host plants. To understand the genetic diversity and molecular epidemiology of this fungus, we have developed a novel, high-resolution multi-locus microsatellite typing (MLMT) method. Bioinformatic analysis of C. gloeosporioides unannotated genome sequence yielded eight potential microsatellite loci, of which five, CG1 (GT)(n), CG2 (GT1)(n), CG3 (TC)(n), CG4 (CT)(n), and CG5 (CT1)(n) were selected for further study based on their universal amplification potential, reproducibility, and repeat number polymorphism. The selected microsatellites were used to analyze 31 strains of C. gloeosporioides isolated from 20 different host plants from India. All microsatellite loci were found to be polymorphic, and the approximate fragment sizes of microsatellite loci CG1, CG2, CG3, CG4, and CG5 were in ranges of 213–241, 197–227, 231–265, 209–275, and 132–188, respectively. Among the 31 isolates, 55 different genotypes were identified. The Simpson's index of diversity (D) values for the individual locus ranged from 0.79 to 0.92, with the D value of all combined five microsatellite loci being 0.99. Microsatellite data analysis revealed that isolates from Ocimum sanctum, Capsicum annuum (chili pepper), and Mangifera indica (mango) formed distinct clusters, therefore exhibited some level of correlation between certain genotypes and host. The developed MLMT method would be a powerful tool for studying the genetic diversity and any possible genotype-host correlation in C. gloeosporioides.
		                        		
		                        		
		                        		
		                        			Capsicum
		                        			;
		                        		
		                        			Colletotrichum*
		                        			;
		                        		
		                        			Computational Biology
		                        			;
		                        		
		                        			Fungi
		                        			;
		                        		
		                        			Genetic Variation
		                        			;
		                        		
		                        			Genome
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			India
		                        			;
		                        		
		                        			Mangifera
		                        			;
		                        		
		                        			Methods*
		                        			;
		                        		
		                        			Microsatellite Repeats*
		                        			;
		                        		
		                        			Molecular Epidemiology
		                        			;
		                        		
		                        			Ocimum
		                        			;
		                        		
		                        			Statistics as Topic
		                        			
		                        		
		                        	
10.Frequency of group A rotavirus with mixed G and P genotypes in bovines: predominance of G3 genotype and its emergence in combination with G8/G10 types.
Yashpal S MALIK ; Kuldeep SHARMA ; Nirupama VAID ; Somendu CHAKRAVARTI ; K M CHANDRASHEKAR ; Sanjay S BASERA ; Rashmi SINGH ; MINAKSHI ; Gaya PRASAD ; Baldev R GULATI ; Kiren N BHILEGAONKAR ; Awadh B PANDEY
Journal of Veterinary Science 2012;13(3):271-278
		                        		
		                        			
		                        			The present study describes the genotypic distribution of rotaviruses (RVs) in an Indian bovine population with unexpectedly higher proportions of G3 alone or in combination of G8/G10. PCR-genotyping confirmed that 39.4% (13/33) of the prevalent RVs were the G3 type while 60.6% (20/33) were dual G3G10 or G3G8 types. P typing revealed that 93.9% (31/33) of the samples were P[11] while 6.1% (2/33) possessed a dual P[1]P[11] type. Sequence analysis of the VP7 gene from G3 strains viz. B-46, 0970, and BR-133 showed that these strains had sequence identities of 90.5% to 100% with other bovine G3 strains. The highest identity (98.9% to 100%) was observed with RUBV3 bovine G3 strains from eastern India. The G3 strains (B-46, 0970, and BR-133) showed 97.5% to 98.8% sequence homologies with the Indian equine RV strain Erv-80. Phylogenetic analysis demonstrated that G3 strains clustered with bovine RUBV3 and J-63, and equine Erv-80 G3. Overall, these results confirmed that the incidence of infection by RVs with the G3 genotype and mixed genotypes in the bovine population was higher than previously predicted. This finding reinforces the importance of constantly monitoring circulating viral strains with the G3 genotype in future surveillance studies.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Cattle
		                        			;
		                        		
		                        			Cattle Diseases/epidemiology/*virology
		                        			;
		                        		
		                        			Desert Climate
		                        			;
		                        		
		                        			Feces/virology
		                        			;
		                        		
		                        			Genotype
		                        			;
		                        		
		                        			India/epidemiology
		                        			;
		                        		
		                        			Molecular Sequence Data
		                        			;
		                        		
		                        			Phylogeny
		                        			;
		                        		
		                        			RNA, Viral/genetics
		                        			;
		                        		
		                        			Reverse Transcriptase Polymerase Chain Reaction/veterinary
		                        			;
		                        		
		                        			Rotavirus/classification/*genetics/isolation & purification
		                        			;
		                        		
		                        			Rotavirus Infections/epidemiology/*veterinary/virology
		                        			;
		                        		
		                        			Sequence Analysis, Protein/veterinary
		                        			;
		                        		
		                        			Sequence Analysis, RNA/veterinary
		                        			;
		                        		
		                        			Sequence Homology
		                        			;
		                        		
		                        			Tropical Climate
		                        			
		                        		
		                        	
            
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