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Article ; Online: Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection.

Aggerbeck, Henrik / Giemza, Rafaela / Joshi, Paulatsya / Tingskov, Pernille N / Hoff, Søren T / Boyle, Julia / Andersen, Peter / Lewis, David J M

PloS one

2013 Volume 8, Issue 5, Page(s) e64215

Abstract: ... of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection ... Methods: In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected ... specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD ...

Abstract	Background: Tuberculin skin testing is simple and relatively inexpensive, but the specificity of PPD is affected by BCG vaccination. Objective: Determine optimal dose and specificity of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection. Methods: In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected by Mantoux technique in 38 patients with active tuberculosis and induration responses measured. In a phase II specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD. Results: 0.1 µg C-Tb gave a median induration of 15 mm after 2 days. Phenol preservation did not affect the response. The specificity of C-Tb was 99.3% (95% CI 96-100%) regarding indurations ≥5 mm as a positive outcome. This was higher than the specificity of PPD (63% using a cut-off of 5 mm or 92% using a cut-off of 15 mm to adjust for non-specific BCG responses). Local adverse reactions following C-Tb injection included transient itching and discomfort as expected components of the immune response. Conclusion: C-Tb offers a simple and convenient skin test to diagnose M. tuberculosis infection using a single, universal cut-off unaffected by BCG vaccination. Trial registration: ClinicalTrials.gov NCT01033929 and NCT01241188.
MeSH term(s)	Adolescent ; Adult ; Antigens, Bacterial/adverse effects ; Antigens, Bacterial/chemistry ; Antigens, Bacterial/immunology ; Bacterial Proteins/adverse effects ; Bacterial Proteins/chemistry ; Bacterial Proteins/immunology ; Dose-Response Relationship, Immunologic ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium bovis/immunology ; Mycobacterium tuberculosis/immunology ; Mycobacterium tuberculosis/physiology ; Phenol/chemistry ; Sensitivity and Specificity ; Tuberculin Test/adverse effects ; Tuberculin Test/methods ; Tuberculosis/diagnosis ; Tuberculosis/immunology ; Vaccination ; Young Adult
Chemical Substances	Antigens, Bacterial ; Bacterial Proteins ; CFP-10 protein, Mycobacterium tuberculosis ; ESAT-6 protein, Mycobacterium tuberculosis ; Phenol (339NCG44TV)
Language	English
Publishing date	2013-05-14
Publishing country	United States
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0064215
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Article: The loop C region of the murine 5-HT3A receptor contributes to the differential actions of 5-hydroxytryptamine and m-chlorophenylbiguanide.

Suryanarayanan, Asha / Joshi, Prasad R / Bikádi, Zsolt / Mani, Muthalagi / Kulkarni, Trupti R / Gaines, Chandra / Schulte, Marvin K

Biochemistry

2005 Volume 44, Issue 25, Page(s) 9140–9149

Abstract: ... to investigate the role of amino acids from the loop C region of the murine 5-HT(3AS)R in interacting with two ... structurally different agonists, serotonin (5-HT) and m-chlorophenylbiguanide (mCPBG). Mutant receptors were ... interaction of these ligands with loop C. Residues F226 and Y234 are important for both 5-HT and mCPBG ...

Abstract	Sequence and predicted structural similarities between members of the Cys loop superfamily of ligand-gated ion channel receptors and the acetylcholine binding protein (AChBP) suggest that the ligand-binding site is formed by six loops that intersect at subunit interfaces. We employed site-directed mutagenesis to investigate the role of amino acids from the loop C region of the murine 5-HT(3AS)R in interacting with two structurally different agonists, serotonin (5-HT) and m-chlorophenylbiguanide (mCPBG). Mutant receptors were evaluated using radioligand binding, two-electrode voltage clamp, and immunofluorescence studies. Electrophysiological assays were employed to identify changes in response characteristics and relative efficacies of mCPBG and the partial agonist, 2-methyl 5-HT (2-Me5-HT). We have also constructed novel 5-HT and mCPBG docked models of the receptor binding site based on homology models of the AChBP. Both ligand-docked models correlate well with results from mutagenesis and electrophysiological assays. Four key amino acids were identified as being important to ligand binding and/or gating of the receptor. Among these, I228 and D229 are specific for effects mediated by 5-HT compared to mCPBG, indicating a differential interaction of these ligands with loop C. Residues F226 and Y234 are important for both 5-HT and mCPBG interactions. Mutations at F226, I228, and Y234 also altered the relative efficacies of agonists, suggesting a role in the gating mechanism.
MeSH term(s)	Amino Acid Sequence ; Animals ; Biguanides/chemistry ; Biguanides/metabolism ; Cell Line ; Electrophysiology ; Humans ; Methylation ; Mice ; Models, Molecular ; Mutation/genetics ; Oocytes/metabolism ; Patch-Clamp Techniques ; Protein Structure, Tertiary ; Radioligand Assay ; Receptors, Serotonin, 5-HT3/chemistry ; Receptors, Serotonin, 5-HT3/genetics ; Receptors, Serotonin, 5-HT3/metabolism ; Sequence Alignment ; Serotonin/chemistry ; Serotonin/metabolism ; Serotonin 5-HT3 Receptor Agonists ; Serotonin Receptor Agonists/chemistry ; Serotonin Receptor Agonists/metabolism ; Xenopus laevis
Chemical Substances	Biguanides ; Receptors, Serotonin, 5-HT3 ; Serotonin 5-HT3 Receptor Agonists ; Serotonin Receptor Agonists ; Serotonin (333DO1RDJY) ; 1-(3-chlorophenyl)biguanide (910A4X901V)
Language	English
Publishing date	2005-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi050661e
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Article: Consumer grievance reporting in G.M.C. Hospital, Miraj.

Yadav, J U / Joshi, J K / Kumbhar, S K

Indian journal of public health

2007 Volume 51, Issue 1, Page(s) 68–69

Abstract: A cross-sectional study conducted among 400 'consumers' at G.M.C. Hospital, Miraj revealed 91 ...

Abstract	A cross-sectional study conducted among 400 'consumers' at G.M.C. Hospital, Miraj revealed 91% consumers had one/more grievance/s. Higher grievances reported in illiterates, lower social class, indoor patients, surgical patients. Lower grievances reported in age < 15 yrs and 31-45 yrs, rural dwellers. Sex and new / old status of patients not affected grievance- reporting. 10 grievances out of 38 were found to be of serious nature. Some grievances (e.g. post-operative complications, discharge without clinical relief, absence of counselling, cursory clinical examination etc.) might have potential as possible medical negligence.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Cross-Sectional Studies ; Female ; Hospital Administration ; Humans ; India ; Male ; Malpractice ; Middle Aged ; Patient Satisfaction ; Sex Factors ; Socioeconomic Factors
Language	English
Publishing date	2007-01
Publishing country	India
Document type	Journal Article
ZDB-ID	800737-8
ISSN	2229-7693 ; 0019-557X
ISSN (online)	2229-7693
ISSN	0019-557X
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Article ; Online: Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection.

Henrik Aggerbeck / Rafaela Giemza / Paulatsya Joshi / Pernille N Tingskov / Søren T Hoff / Julia Boyle / Peter Andersen / David J M Lewis

PLoS ONE, Vol 8, Iss 5, p e

2013 Volume 64215

Abstract: ... ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection ... METHODS: In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected ... specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD. RESULTS ...

Abstract	BACKGROUND: Tuberculin skin testing is simple and relatively inexpensive, but the specificity of PPD is affected by BCG vaccination. OBJECTIVE: Determine optimal dose and specificity of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection. METHODS: In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected by Mantoux technique in 38 patients with active tuberculosis and induration responses measured. In a phase II specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD. RESULTS: 0.1 µg C-Tb gave a median induration of 15 mm after 2 days. Phenol preservation did not affect the response. The specificity of C-Tb was 99.3% (95% CI 96-100%) regarding indurations ≥5 mm as a positive outcome. This was higher than the specificity of PPD (63% using a cut-off of 5 mm or 92% using a cut-off of 15 mm to adjust for non-specific BCG responses). Local adverse reactions following C-Tb injection included transient itching and discomfort as expected components of the immune response. CONCLUSION: C-Tb offers a simple and convenient skin test to diagnose M. tuberculosis infection using a single, universal cut-off unaffected by BCG vaccination. TRIAL REGISTRATION: ClinicalTrials.gov NCT01033929 and NCT01241188.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Re: a novel drug eluting ureteral stent: a prospective, randomized, multicenter clinical trial to evaluate the safety and effectiveness of a ketorolac loaded ureteral stent: A. E. Krambeck, R. S. Walsh, J. D. Denstedt, G. M. Preminger, J. Li, J. C. Evans and J. E. Lingeman J Urol 2010; 183: 1037-1043.

Joshi, H B / Keeley, F X / Timoney, A G

The Journal of urology

2010 Volume 184, Issue 5, Page(s) 2217–8; author reply 2218

MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Drug-Eluting Stents/adverse effects ; Humans ; Ketorolac/administration & dosage ; Multicenter Studies as Topic ; Pain/drug therapy ; Pain/etiology ; Prospective Studies ; Prosthesis Design ; Randomized Controlled Trials as Topic ; Ureter/surgery
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Ketorolac (YZI5105V0L)
Language	English
Publishing date	2010-11
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	3176-8
ISSN	1527-3792 ; 0022-5347
ISSN (online)	1527-3792
ISSN	0022-5347
DOI	10.1016/j.juro.2010.06.124
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Article ; Online: Digital PCR: A Partitioning-Based Application for Detection and Surveillance of SARS-CoV-2 from Sewage Samples.

Prajapati, Bhumika / Rathore, Dalipsingh / Joshi, Chaitanya / Joshi, Madhvi

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2967, Page(s) 1–16

Abstract: The wastewater-based surveillance of SARS-CoV-2 has emerged as a potential tool for cost-effective, simple, and long-term monitoring of the pandemic. Since the COVID-19 pandemic, several developed countries have incorporated the national wastewater ... ...

Abstract	The wastewater-based surveillance of SARS-CoV-2 has emerged as a potential tool for cost-effective, simple, and long-term monitoring of the pandemic. Since the COVID-19 pandemic, several developed countries have incorporated the national wastewater surveillance program into their national policies related to pandemic management. Various research groups have utilized the approach of real-time quantitative reverse transcription PCR (RT-qPCR) for the quantification of SARS-CoV-2 from environmental samples like sewage water. However, detection and quantification using RT-qPCR relies on standards and is known to have lesser tolerance to inhibitors present in the sample. Unlike RT-qPCR, digital PCR (dPCR) offers an absolute and sensitive quantification without a need reference and offers higher tolerance to inhibitors present in the wastewater samples. Additionally, the accuracy of detection increases with the presence of rare target copies in the sample. The methodology herein presented comprises the detection and quantification of SARS-CoV-2 from sewer shed samples using the dPCR approach. The main features of the process include virus concentration and absolute quantification of the virus surpassing the substantial presence of inhibitors in the sample. This chapter presents the optimized PEG and NaCl-based protocol for virus concentration followed by nucleic acid extraction and quantification using CDC-approved N1 + N2 assay. The protocol uses MS2 bacteriophage as a process recovery or internal control.The methodology herein described highlights the importance of digital PCR technologies for environmental surveillance of important emerging pathogens or pandemics.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; Sewage ; Wastewater ; Pandemics ; COVID-19/diagnosis ; COVID-19/epidemiology ; Wastewater-Based Epidemiological Monitoring ; Real-Time Polymerase Chain Reaction ; COVID-19 Testing
Chemical Substances	Sewage ; Wastewater
Language	English
Publishing date	2023-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3358-8_1
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Article ; Online: A study into the diversity of coral-associated bacteria using culture-dependent and culture-independent approaches in coral Dipsastraea favus from the Gulf of Kutch.

Patel, Zarna Z / Joshi, Himanshu / Puvar, Apurvasinh / Pandit, Ramesh / Joshi, Chaitanya / Joshi, Madhvi / Tipre, Devayani R

Marine pollution bulletin

2024 Volume 201, Page(s) 116172

Abstract: Corals harbour ~25 % of the marine diversity referring to biodiversity hotspots in marine ecosystems. Global efforts to find ways to restore the coral reef ecosystem from various threats can be complemented by studying coral-associated bacteria. Coral- ... ...

Abstract	Corals harbour ~25 % of the marine diversity referring to biodiversity hotspots in marine ecosystems. Global efforts to find ways to restore the coral reef ecosystem from various threats can be complemented by studying coral-associated bacteria. Coral-associated bacteria are vital components of overall coral wellbeing. We explored the bacterial diversity associated with coral Dipsastraea favus (D. favus) collected from the Gulf of Kutch, India, using both culture-dependent and metagenomic approaches. In both approaches, phylum Proteobacteria, Firmicutes, and Actinobacteria predominated, comprising the genera Vibrio, Bacillus, Shewanella, Pseudoalteromonas, Exiguobacterium and Streptomyces. Moreover, the majority of culturable isolates showed multiple antibiotic resistance index ≥0.2. In this study, specific bacterial diversity associated with coral sp. D. favus and its possible role in managing coral health was established. Almost 43 strains from the samples were successfully cultured, creating a base for exploring these microbes for their potential use in coral conservation methods.
MeSH term(s)	Animals ; Anthozoa/microbiology ; Ecosystem ; Tinea Favosa ; Phylogeny ; RNA, Ribosomal, 16S ; Bacteria/genetics ; Coral Reefs ; Biodiversity
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2024-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2001296-2
ISSN	1879-3363 ; 0025-326X
ISSN (online)	1879-3363
ISSN	0025-326X
DOI	10.1016/j.marpolbul.2024.116172
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Article ; Online: Langmuir Hosts an ACS Connect Symposium in India.

Joshi, Yogesh M / Walker, Gilbert C

Langmuir : the ACS journal of surfaces and colloids

2021 Volume 37, Issue 2, Page(s) 603–604

Language	English
Publishing date	2021-01-18
Publishing country	United States
Document type	Editorial
ZDB-ID	2005937-1
ISSN	1520-5827 ; 0743-7463
ISSN (online)	1520-5827
ISSN	0743-7463
DOI	10.1021/acs.langmuir.0c03612
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Article ; Online: Better Social-emotional Behavior in Young Nepali Children is Associated with Household Wealth, Child Age, and Family Participation in a Community Development Intervention.

Miller, L C / Neupane, S / Shrestha, M / Joshi, N / Lohani, M / Thorne-Lyman, A

Kathmandu University medical journal (KUMJ)

2024 Volume 21, Issue 82, Page(s) 197–206

Abstract: Background Mental health and behavior problems are under-recognized in low- and middleincome countries, especially in young children. Early identification of these problems could encourage governments to address the shortages of child mental health ... ...

Abstract	Background Mental health and behavior problems are under-recognized in low- and middleincome countries, especially in young children. Early identification of these problems could encourage governments to address the shortages of child mental health professionals and promote early intervention programs to help children achieve their full developmental potential. Objective Describe the social-emotional development of young rural Nepali children; explore risk factors for poor development. Method The study was embedded in a longitudinal intervention trial comparing control households with those who received training in family nutrition+livestock management (Partial Package) or family nutrition+livestock management+community mobilization (Full Package). At midline, enumerators completed a 145-item household questionnaire, child anthropometry, and Administered the Ages and Stages Questionnaire-Social-Emotional (ASQ-SE) to all enrolled children age 33-47 months (n=310). Bivariate and regression analyses examined the relationship of child and household risk factors to administered the Ages and Stages QuestionnaireSocial-Emotional scores. Result Administered the Ages and Stages Questionnaire-Social-Emotional scores were below age cutoffs in 24% of children, suggesting worse social-emotional development. In bivariate analyses and the adjusted linear regression model, older child age, greater household wealth, and Full Package Intervention status were all associated with better social-emotional development scores. Partial Package Intervention status was associated with worse scores. Conclusion The Administered the Ages and Stages Questionnaire-Social-Emotional is a potential tool to assess child social-emotional development in the context of household and community level interventions. Further work is necessary to validate the administered the Ages and Stages Questionnaire-Social-Emotional and similar tools in Nepal, and to better understand the prevalence of challenges to optimal socialemotional development in young children in order to use this information to design and monitor needed interventions.
MeSH term(s)	Child, Preschool ; Humans ; Child Development ; Nepal ; Risk Assessment ; Socioeconomic Factors ; Surveys and Questionnaires
Language	English
Publishing date	2024-04-08
Publishing country	Nepal
Document type	Journal Article
ZDB-ID	2257651-4
ISSN	1812-2078 ; 1812-2078
ISSN (online)	1812-2078
ISSN	1812-2078
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Article ; Online: RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms.

Joshi, Ilin V / Chan, Eunice C / Lack, Justin B / Liu, Chengyu / Druey, Kirk M

The Journal of biological chemistry

2024 Volume 300, Issue 4, Page(s) 107127

Abstract: Regulators of G protein signaling (RGS) proteins constrain G protein-coupled receptor (GPCR)-mediated and other responses throughout the body primarily, but not exclusively, through their GTPase-activating protein activity. Asthma is a highly prevalent ... ...

Abstract	Regulators of G protein signaling (RGS) proteins constrain G protein-coupled receptor (GPCR)-mediated and other responses throughout the body primarily, but not exclusively, through their GTPase-activating protein activity. Asthma is a highly prevalent condition characterized by airway hyper-responsiveness (AHR) to environmental stimuli resulting in part from amplified GPCR-mediated airway smooth muscle contraction. Rgs2 or Rgs5 gene deletion in mice enhances AHR and airway smooth muscle contraction, whereas RGS4 KO mice unexpectedly have decreased AHR because of increased production of the bronchodilator prostaglandin E2 (PGE2) by lung epithelial cells. Here, we found that knockin mice harboring Rgs4 alleles encoding a point mutation (N128A) that sharply curtails RGS4 GTPase-activating protein activity had increased AHR, reduced airway PGE2 levels, and augmented GPCR-induced bronchoconstriction compared with either RGS4 KO mice or WT controls. RGS4 interacted with the p85α subunit of PI3K and inhibited PI3K-dependent PGE2 secretion elicited by transforming growth factor beta in airway epithelial cells. Together, these findings suggest that RGS4 affects asthma severity in part by regulating the airway inflammatory milieu in a G protein-independent manner.
MeSH term(s)	Animals ; RGS Proteins/metabolism ; RGS Proteins/genetics ; Mice ; Dinoprostone/metabolism ; Asthma/metabolism ; Asthma/genetics ; Asthma/pathology ; Mice, Knockout ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/metabolism ; Humans ; Respiratory Hypersensitivity/metabolism ; Respiratory Hypersensitivity/genetics ; Respiratory Hypersensitivity/pathology ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Bronchoconstriction
Chemical Substances	RGS Proteins ; RGS4 protein (175335-35-0) ; Dinoprostone (K7Q1JQR04M) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; GTPase-Activating Proteins
Language	English
Publishing date	2024-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2024.107127
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