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1.
PLoS One ; 19(3): e0301060, 2024.
Article in English | MEDLINE | ID: mdl-38536792

ABSTRACT

BACKGROUND: Tuberculosis (TB) continues to pose a significant public health challenge in India, which is home to one of the highest TB burdens worldwide. This systematic review and meta-analysis will aim to synthesize the anticipated progress and potential challenges in achieving TB elimination in India by 2025. METHODS: A comprehensive search will be conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify relevant studies. The eligibility criteria will encompass individuals diagnosed with TB in India, interventions targeting TB treatment, prevention, or control, and various comparator groups. Outcomes of interest will include incidence reduction, mortality rate, treatment success rate, barriers to TB care, and more. Both quantitative and qualitative data will be synthesized, and the risk of bias will be assessed using established tools. OUTCOMES: The review is expected to provide a holistic understanding of the TB landscape in India, highlighting the effective interventions and potential challenges in the journey towards TB elimination. CONCLUSIONS: While it is anticipated that significant progress will be made in the fight against TB in India, challenges are likely to persist. This review will offer a comprehensive roadmap for researchers, policymakers, and healthcare professionals, emphasizing the importance of continued efforts, innovative strategies, and a multi-pronged approach in achieving the goal of TB elimination in India by 2025.


Subject(s)
Tuberculosis , Humans , Tuberculosis/epidemiology , Tuberculosis/prevention & control , Incidence , India/epidemiology
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 313: 124092, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38457871

ABSTRACT

Pyrazoles have recently received significant attention due to their unique and potential applications in the medical field, agriculture and are also known to be highly stable explosives. The present work describes the terahertz time-domain spectroscopy (THz-TDS) based study of 4-Amino 3,5 Dinitro Pyrazole(ADNP) in between the 0.1 and 3.0 THz ranges. A Toptica-Teraflash fibre-coupled handheld terahertz system has been employed in reflection mode configuration. We ascertained complex refractive index, absorption coefficients, and complex dielectric constants from 0.1 THz to 3.0 THz. The value of the refractive index and absorption coefficients are found to be 1.8 and 10---180 cm -1, respectively. Also, we have analyzed the structural, vibrational, and optical properties of ADNP using the plane-wave pseudopotential method based on Density Functional Theory (DFT) calculations. We have observed six low-frequency optical phonon modes, located at 0.36, 1.20, 1.52, 1.77, 2.40, and 2.75 THz, respectively, exhibiting a redshift compared to the values predicted by the DFT calculations. The possible reasoning for the above might be due to the anharmonicity that is not considered in the DFT calculations. The theoretical calculations align with the experimental results and deliver direction for further investigations and the futuristic application of ADNP.

3.
Access Microbiol ; 6(1)2024.
Article in English | MEDLINE | ID: mdl-38361657

ABSTRACT

This paper elucidates the transformative impact of a strategic shift in diagnostic practices in the detection of Trichomonas vaginalis. It explores five cases where the implementation of a specific diagnostic protocol led to effective identification of the infection. In-depth discussions and a comprehensive literature review underline the necessity for precise diagnosis and the paramount importance of diagnostic stewardship in managing sexually transmitted infections.

4.
Eval Program Plann ; 97: 102230, 2023 04.
Article in English | MEDLINE | ID: mdl-36702005

ABSTRACT

Identifying the effectiveness of agricultural interventions is a challenge faced by many international aid initiatives. This article reports on our efforts to document the success of agricultural aid interventions. The study is focused on evaluating cacao projects in Colombia, specifically on assessing the success of the rural Productive Partnerships Project (PAAP). The two approaches used to assess the project's success included the degree of accomplishment of four of the PAAP project's objectives and a measurement of the project performance at the local level, for which an existing performance index was utilized. Quantitative data were obtained from the project's evaluation platform developed by the PAAP project coordinators. Based on our first evaluation approach, we found that the four project objectives evaluated were not fully accomplished. While our results using the performance index provide baseline data for upcoming work assessing cacao projects' performance, the absence of precedent information constrained its interpretation. Finally, the paper offers feasible, affordable, and practical recommendations that could benefit future program planning and evaluation of international aid interventions, particularly on cacao projects worldwide.


Subject(s)
Cacao , Humans , Colombia , Program Evaluation , Program Development
5.
J Family Med Prim Care ; 11(4): 1493-1496, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35516678

ABSTRACT

Introduction: SARS COVID-19 infection leads to wide range of symptoms in comorbid pediatric patient. In view of its susceptibility affecting pediatric age groups with comorbidities and its potential to increase the mortality rate, it may have adverse effects on the outcome of such children. This study aims at better understanding of clinical profile and its outcome of pediatric population. Method: A total of 50 pediatric patients aged 1 to 17 years with comorbidities and laboratory confirmed COVID-19 that were admitted at the RIMS, Ranchi from 1st April 2020 to 31st December 2020 were studied. Result: 34 (68%) resided in the hot spot areas of the region, 8(16%) resided in the non- hot spot areas and 8(16%) had migrated from elsewhere. Higher proportion of males between 11-15 years of age were affected (64%).Our study shows that the majority of the children that were affected were of the age group 11-15 years (52%). 38(76%) of these children presented with fever as their major complaints, cough in 28(56%), sore throat in 2 (4%), diarrhea in 6(12%), vomiting in 11 (22%), breathing difficulty in 20 (50%) and 30 (60%) had other symptoms. Out of 50 patients admitted, 3 died. In our study majority of comorbid condition was thalassemia major. Conclusion: The presenting characteristics, comorbidities, and severity of illness of pediatric patients with COVID-19 were different, and milder, compared with adults.

6.
J Family Med Prim Care ; 11(3): 1026-1031, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35495798

ABSTRACT

Objective: The objective of this article is to study the impact of coronavirus disease 2019 (COVID-19) pandemic first wave on the in-hospital length of stay of operated proximal femur fractures. Materials and Methods: A retrospective analysis of data collected through the electronic record system of the hospital, after applying inclusion and exclusion criteria, was done. The data were collected from the pre-pandemic, early part first wave and later part first wave of COVID-19 pandemic to calculate the average preoperative stay (POS) and total length of stay (LOS) of operated proximal femur fracture patients. Also, a sub-analysis of POS and LOS was done as per age (male/female), sex (<60/≥60 years) and fracture subtype (intertrochanteric, neck of femur and subtrochanteric fracture) of the patients to study if any of these had a significant direct impact on the POS and LOS. Results: The LOS and POS were found to be significantly increased during early part of first wave of COVID-19 pandemic in comparison to the pre-pandemic era (13.6 ± 7.7 days vs. 11.1 ± 5.7 days). The later part of the first wave of the pandemic however saw the LOS and POS to return to near pre-pandemic values, although still remaining higher. Conclusion: The study highlights that unpreparedness during the early part of the unprecedented pandemic event leads to a significant increase in LOS of operated patients with its associated implications; however, prompt action by the government, hospital administration and hospital staff the LOS could be reduced to near pre-pandemic values in the later part of the first wave of the pandemic. Analysis of the causes that lead to a significant increase in LOS can help for better future management of similar events in future.

7.
J Family Med Prim Care ; 11(11): 7163-7167, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36993015

ABSTRACT

Background: A diphtheria outbreak occurred in Banaskantha district in the northern part of Gujarat in 2019-2020. This study was undertaken to study and generate information on the resurgence of the disease in this region and to generate information regarding the status of vaccination in this region and what strategies can be adopted to avoid re-emergence of the disease in the future. Materials and Methods: This is a hospital-based, retrospective, descriptive study done on patients of diphtheria who were admitted in Banas Medical College and Research Institute, Palanpur from September 2019 to January 2020. Throat swab was taken from all the patients and information regarding symptoms, vaccination, and demographic characteristic was collected. Treatment in the form of ADS, injection crystalline penicillin/erythromycin and other supportive treatment was given. Result: Out of 188 patients, 27 patients (14.36%) were less than 5 years of age, 118 patients (62.76%) and 38 patients (20.21%) were of age group 5-10 and 11-18 years, respectively. Total of five patients (2.66%) were of age more than 18 years. Out of 188 patients, 102 (54.25%) were males and 86 patients (45.74%) were females. All the patients (188) were found to be unvaccinated. Among 188 throat swabs that were tested, 21 samples (11.17%) were found to be culture positive for Corynebacterium diphtheriae. Antidiphtheric serum was given in 181 patients (96.27%) according to the requirement. Out of 188 patients, 155 patients (82.44%) improved with treatment and were discharged. Total of 23 patients (12.23%) were referred to higher center for tracheostomy and for management of other complications. Six patients (3.19%) left against medical advice and four patients (2.12%) expired despite all measures taken. Conclusion: Diphtheria is a disease that can easily be prevented by vaccination. Our study highlights need to increase awareness about vaccination among people of Banaskatha district and all measures should be taken to give full vaccination to children less than 5 years of age and booster vaccination should be encouraged in adolescents and adults so that future resurgence of disease can be prevented.

8.
J Colloid Interface Sci ; 586: 39-46, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33189326

ABSTRACT

The artificial stacking of nanohybrid films helps to enhance their properties and thus intrigues researchers to explore this possibility in emerging technologies. The layer-by-layer approach was used to fabricate samples of zinc sulfide/reduced graphene oxide (ZnS/rGO) by using spin coating technique. The structure and optoelectronic properties has been extensively studied by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), UV-VIS-NIR spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Hall measurements. Raman spectrum elucidates the phonon contribution of ZnS and breathing mode of κ-point phonons and sp2 bonds of carbon atoms of rGO. The electron-phonon interactions reveal reduction in electron mobility and enhancement in holes contribution with rGO content leading to surface charge transfer doping (SCTD). XPS results explain the valence band edge and conduction band edge to form type-I band alignment to reconfirm carrier-type reversal. A change in the dispersion of refractive indices along with a small rise in the value of absorption coefficient in terahertz (THz) region for ZnS/rGO nanocomposite films has been observed. These results will open up new opportunities to furthering the science of this technologically important class of materials for future electronics.

9.
ACS Omega ; 5(6): 2541-2551, 2020 Feb 18.
Article in English | MEDLINE | ID: mdl-32095678

ABSTRACT

The paper reports the time-domain THz spectroscopy studies of noncentrosymmetric energetic nitro/nitrogen-rich aryl-tetrazole high-energy molecules. The fingerprint spectra in the THz domain reveal the role of different functional groups attached to position "1" of the tetrazole moiety, which controls the energetic properties. These responses are deliberated through density functional theory (DFT) calculations. The synthesized aryl-tetrazoles exhibit high positive heat of formation (369-744 kJ/mol), high detonation velocities, and pressures (D v: 7734-8298 m·s-1; D p: 24-28 GPa) in comparison to the noncentrosymmetric 2,4,6-trinitrotoluene (TNT). These compounds exhibit variation in the refractive indices and absorption between 0.1 and 2.2 THz range. The DFT studies at the molecular and single-crystal level (using plane wave pseudo potential method) endorse in detecting these bands (with ∼1% deviation). The calculated vibrational frequencies and linear optical properties are found to have good agreement with the experimental data in UV-visible and THz regions.

10.
Eval Program Plann ; 79: 101790, 2020 04.
Article in English | MEDLINE | ID: mdl-32036322

ABSTRACT

The overlap of competencies between general program evaluation and specific contexts or content will always be reality because evaluators may need unique competencies to answer evaluation questions for particular contexts or content areas. Limited research exists that explores the essential competencies required by professionals who use evaluation as one part of their job portfolio, which leaves unanswered questions regarding the applicability of current evaluator competency models in such settings. We used a modified three-round Delphi technique to identify evaluator competencies for non-formal educators in Cooperative Extension (CE). Our panelists identified 36 competencies in the non-formal educational programming context for CE educators that they considered important to be included in evaluation capacity building efforts. We categorized our 36 identified competencies from the Delphi study into the five competency domains proposed by the American Evaluation Association. Our findings provide information to help guide professional development among non-formal educators related to program evaluation.


Subject(s)
Education, Professional/organization & administration , Professional Competence/standards , Program Evaluation/methods , Delphi Technique , Education, Professional/standards , Humans , Problem-Based Learning , Program Evaluation/standards
11.
Eval Program Plann ; 79: 101768, 2020 04.
Article in English | MEDLINE | ID: mdl-31958716

ABSTRACT

Policymakers' demand for increased accountability has compelled organizations to pay more attention to internal evaluation capacity building (ECB). The existing literature about ECB has focused on capacity building experiences and organizational research, with limited attention on challenges that internal evaluation specialists face in building organizational evaluative capacity. To address this knowledge gap, we conducted a Delphi study with evaluation specialists in the United States' Cooperative Extension Service and developed a consensus on the most pervasive ECB challenges as well as the most useful strategies for overcoming ECB challenges. Challenges identified in this study include limited time and resources, limited understanding of the value of evaluation, evaluation considered as an afterthought, and limited support and buy-in from administrators. Alternatively, strategies found in the study include a shift in an organizational culture where evaluation is appreciated, buy-in and support from administration, clarifying the importance of quality than quantity of evaluations, and a strategic approach to ECB. The challenges identified in this study have persisted for decades, meaning administrators must understand the persistence of these issues and make an earnest investment (financial and human resource) to make noticeable progress. The Delphi approach can be used more often to prioritize ECB efforts.


Subject(s)
Capacity Building/organization & administration , Program Evaluation/methods , Universities/organization & administration , Capacity Building/standards , Delphi Technique , Humans , Leadership , Organizational Culture , Time Factors , United States , Universities/standards , Work Engagement
12.
Chin J Traumatol ; 22(5): 274-277, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31362854

ABSTRACT

PURPOSE: Shoulder dislocation comprises 60% of all major joint dislocations worldwide and a number of reduction techniques are described in the literature with varying degrees of success. The description of a large number of techniques speaks for itself that no method is effective all the times and one should be acquainted with more than one technique. An ideal method of reduction should be simple, easily reproducible, relatively painless that can be performed unassisted without sedation or anaesthesia with minimal or no further complications. We report our results of using a novel method of anterior shoulder reduction described recently in the literature that claims to fulfil most of the characteristics of an ideal method if not all. METHODS: This prospective study was conducted in a tertiary care centre. All the cases of primary anterior shoulder dislocation presenting within three days of injury without any associated fracture or spine trauma with or without greater tuberosity fracture were included. The reduction was done using a novel method by orthopaedic residents in all cases. The need for a second reduction attempt or anaesthesia was considered a treatment failure. Time taken for reduction, pain felt during reduction and complications if any were noted. RESULTS: There were 47 (77.04%) males and 14 (22.95%) females with a mean age of (37.04 ± 12.63) years. The new technique was effective in locating a shoulder dislocation on the first attempt in 58 of the 61 dislocated shoulders (95.08%). The remaining three shoulders were reduced on second attempt by the same technique. Sedative, pre-medication or anaesthesia was not used in any case. The average time taken for the shoulder reduction was (130.5 ± 25.8) seconds and confidence interval (95%) 124-137 s. Iatrogenic complications were not seen in any of the patients. CONCLUSION: This relatively painless technique of shoulder reduction is easy to acquire and practice in emergency department. The advantages of this manoeuvre and its associated safety may justly lead surgeons to select it as their primary method for reduction of anterior shoulder dislocations.


Subject(s)
Manipulation, Orthopedic/methods , Shoulder Dislocation/therapy , Adult , Anesthesia , Emergency Medical Services , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Young Adult
13.
RSC Adv ; 9(65): 38246-38256, 2019 Nov 19.
Article in English | MEDLINE | ID: mdl-35541825

ABSTRACT

This work reports new findings on the formation of a pearl-necklace pattern in self-assembled upconverting nanocrystals (UCN-PNs) which exhibit strong upconversion emission under an NIR excitation source of a femtosecond laser (Fs-laser). Each nano-necklace consists of several upconversion nanoparticles (UCNPs) having a size ca. 10 ± 1 nm. UCN-PNs are arranged in a self-organized manner to form necklace type chains with an average length of 140 nm of a single row of nanoparticles. Furthermore, UCN-PNs are comprised of UCNPs with an average interparticle separation of ca. 4 nm in each of the nanonecklace chains. Interestingly, these UCN-PNs exhibit high energy upconversion especially in the UV region on interaction with a 140 Fs-laser pulse duration at 80 MHz repetition rate and intense blue emission at 450 nm on interaction with a 900 nm excitation source is obtained. The preparation of self-assembled UCNPs is easy and they are very stable for a longer period of time. The emission (fluorescence/luminescence) intensity is very high which can make them unique in innumerable industrial and bio-applications such as for disease diagnosis and therapeutic applications by targeting the infected cells with enhanced efficiency.

14.
Appl Spectrosc ; 71(7): 1481-1493, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28345380

ABSTRACT

We report the comparative study of photoacoustic (PA) fingerprint spectra, thermal decomposition, and stability mechanism of some phenyl and bis series energetic compounds named 1-(2-methoxy,-3,5-dinitrophenyl)-1H-1,2,3-triazole ( S5), 1-(3-methoxy, 2, 6 dinitrophenyl) 1H-1, 2, 3 triazole ( S10), 1-(4-nitrophenyl)-1H-1,2,3-triazole ( S8), and 2,6-bis ((4-(nitromethyl)-1H-1,2,3-triazol-1-yl)methyl) pyridine ( S9). Fourth harmonic wavelength, i.e., 266 nm of pulse duration 7 ns and 10 Hz repetition rate obtained from Q-switched Nd: YAG laser, was used to record the thermal PA spectra of these compounds under controlled pyrolysis condition in the range of 30-350 ℃. The PA fingerprint spectra are produced due to entire molecule vapor along with principal functional byproduct NO2 molecule. NO2 molecule is a major gas released during thermal decomposition due to weakest nature of C-NO2 bond. Further, NO2 molecules are involved in photodissociation process due to π*← n transition and converted into NO molecules inside the PA cell due to excitation by 266 nm wavelength. The combined results of PA and gas chromatography-mass spectrometry (GC-MS) spectra along with thermo gravimetric-differential thermal analysis (TG-DTA) data confirm the thermal decomposition mechanism process that can be completed in multiple steps. In addition, GC-MS spectra also confirm the release of NO and NO2 molecules. The effect of incident laser energy and data acquisition time has been carried out for understanding the behavior of acoustic modes. Finally, the thermal quality factor "Q" is measured to test the stability of compounds.

15.
Cytotechnology ; 68(6): 2553-2565, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27282155

ABSTRACT

The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.

16.
Yonsei Med J ; 57(1): 88-96, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26632387

ABSTRACT

PURPOSE: Diagnosis of extrapulmonary tuberculosis (EPTB) poses serious challenges. A careful selection of appropriate gene targets is essential for designing a multiplex-polymerase chain reaction (M-PCR) assay. MATERIALS AND METHODS: We compared several gene targets of Mycobacterium tuberculosis, including IS6110, devR, and genes encoding MPB-64 (mpb64), 38kDa (pstS1), 65kDa (hsp65), 30kDa (fbpB), ESAT-6 (esat6), and CFP-10 (cfp10) proteins, using PCR assays on 105 EPTB specimens. From these data, we chose the two best gene targets to design an M-PCR. RESULTS: Among all gene targets tested, mpb64 showed the highest sensitivity (84% in confirmed cases and 77.5% in clinically suspected cases), followed by IS6110, hsp65, 38kDa, 30kDa, esat6, cfp10, and devR. We used mpb64+IS6110 for designing an M-PCR assay. Our M-PCR assay demonstrated a high sensitivity of 96% in confirmed EPTB cases and 88.75% in clinically suspected EPTB cases with a high specificity of 100%, taking clinical diagnosis as the gold standard. CONCLUSION: These M-PCR results along with the clinical findings may facilitate an early diagnosis of EPTB patients and clinical management of disease.


Subject(s)
Multiplex Polymerase Chain Reaction/methods , Mycobacterium tuberculosis/isolation & purification , Polymerase Chain Reaction/methods , Tuberculosis/diagnosis , Bacteriological Techniques/methods , DNA Transposable Elements/genetics , DNA, Bacterial/analysis , DNA, Bacterial/genetics , Early Diagnosis , Female , Gene Amplification , Humans , Male , Mycobacterium tuberculosis/genetics , Polymerase Chain Reaction/standards , Sensitivity and Specificity
17.
Diagn Microbiol Infect Dis ; 83(4): 359-64, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26422085

ABSTRACT

We developed a novel indirect sandwich immuno-polymerase chain reaction (I-PCR) assay for the detection of mycobacterial antigen 85B (Ag85B, 30kDa, Rv1886c) in pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients. The amino-modified reporter DNA was covalently attached with the antidetection antibody through a heterobifunctional cross-linking agent succinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate. The detection limit of Ag85B by I-PCR was found to be 1 femtogram (fg)/mL, which was 10(6)-fold lower than an analogous enzyme-linked immunosorbent assay (ELISA). The sensitivities of 85% and 77% with I-PCR and 77.6% and 62.5% with ELISA were observed in smear-positive and smear-negative PTB patients, respectively, with high specificity. On the other hand, sensitivities of 84% and 63.7% with I-PCR and 68% and 47.5% with ELISA were observed in confirmed and clinically suspected EPTB cases, respectively, with high specificity.


Subject(s)
Acyltransferases/analysis , Antigens, Bacterial/analysis , Bacterial Proteins/analysis , Immunoassay/methods , Polymerase Chain Reaction/methods , Tuberculosis/diagnosis , Adolescent , Adult , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Young Adult
18.
Bioorg Med Chem Lett ; 25(22): 5281-5, 2015 Nov 15.
Article in English | MEDLINE | ID: mdl-26428872

ABSTRACT

The 3-substituted oxindole derivatives were designed, synthesized, and evaluated for antidepressant activity by employing forced swimming test, tail suspension test, and MAO-A inhibition assay. Results of biological studies revealed that the majority of compounds exhibited potent to moderately potent activity and among them, 12 displayed potency comparable to that of the imipramine with %DID of 37.95 and 44.84 in the FST and TST, respectively. At the same time, imipramine showed %DID of 43.62 and 50.64 in the FST and TST, correspondingly. In the MAO-A inhibition assay, 12 showed an IC50 of 18.27 µmol, whereas the reference drug moclobemide displayed an IC50 of 13.1 µmol. The SAR study disclosed that the presence of bromo atom at the phenyl/furanyl or thienyl moiety in the oxindole derivatives was critical for the antidepressant activity.


Subject(s)
Antidepressive Agents/chemistry , Benzylidene Compounds/chemistry , Indoles/chemistry , Lactams/chemistry , Monoamine Oxidase Inhibitors/chemistry , Animals , Antidepressive Agents/chemical synthesis , Antidepressive Agents/pharmacology , Benzylidene Compounds/chemical synthesis , Benzylidene Compounds/pharmacology , Clorgyline/pharmacology , Imipramine/pharmacology , Indoles/chemical synthesis , Indoles/pharmacology , Lactams/chemical synthesis , Lactams/pharmacology , Mice , Moclobemide/pharmacology , Molecular Docking Simulation , Monoamine Oxidase/metabolism , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/pharmacology , Structure-Activity Relationship
19.
Sci Rep ; 5: 15214, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26469538

ABSTRACT

Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.


Subject(s)
Gene Expression Profiling , Lymph Nodes/metabolism , Tuberculosis, Lymph Node/pathology , Adolescent , Adult , Child , Cytokines/genetics , Cytokines/metabolism , Epoxide Hydrolases/genetics , Epoxide Hydrolases/metabolism , Fatty Acids/metabolism , Female , Humans , Immunohistochemistry , Lipid Metabolism/genetics , Male , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Proteomics , Real-Time Polymerase Chain Reaction , Th1 Cells/immunology , Th1 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Transcriptome , Tuberculosis, Lymph Node/metabolism
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