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Fulltext Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia

Gadhwal AK, Ankit BS, Chahar C, Tantia P, Sirohi P, Agrawal RP

J Assoc Physicians India, 2016 06;64(6):22-26.
PMID: 27739263

OBJECTIVE: Thrombocytopenia in dengue fever is a common and serious complication. However, no specific treatment is available for dengue fever induced thrombocytopenia. In few countries (Pakistan, Malaysia, Sri Lanka and other Asian countries) the leaf extract of Carica papaya has been effectively used for thrombocytopenia. So, the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients.

METHODS: All participants were randomised into two groups, study group and control group; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days. The controls were given only routine supportive treatment. Daily complete blood counts, platelet counts and haematocrit level, liver function test, renal function test of both groups were observed.

RESULTS: On the first day platelet count of study group and control group was (59.82±18.63, 61.06±20.03 thousands, p value 0.36). On the 2nd day platelet count of both study and control groups was not significantly different (61.67±19.46 and 59.93±19.52 thousands, p value 0.20) but on 3rd day platelet count of study group was significantly higher than control group (82.96±16.72, 66.45±17.36 thousands, p value < 0.01). On 4th and 5th day platelet count of study group (122.43±19.36 and 112.47±17.49 thousands respectively) was also significantly higher than the control group (88.75±21.65 and 102.59±19.35 thousands) (p value < 0.01). On 7th day platelet count of study group and control group were not significantly different (124.47±12.35 and 122.46±19.76 thousands respectively, p value 0.08). Average hospitalization period of study group v/s control group was 3.65±0.97 v/s 5.42±0.98 days (p value < 0.01). Average platelet transfusion requirement in study group was significantly less than control group (0.685 units per patient v/s 1.19 units per patient) (p value <0.01).

CONCLUSIONS: It is concluded that Carica papaya leaf extract increases the platelet count in dengue fever without any side effect and prevents the complication of thrombocytopenia. So, it can be used in dengue fever with thrombocytopenia patients.
Prognosis of oral epithelial dysplasia in individuals with and without oral lichen planus

Pimolbutr K, Lim WT, Leeson R, Hopper C, Kalavrezos N, Liew C, et al.

Oral Dis, 2024 Mar;30(2):504-517.
PMID: 36648368 DOI: 10.1111/odi.14503

OBJECTIVES: To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED).
METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed.
RESULTS: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED), were included. A pre-existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non-cancer-prone sites (p = 0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality.
CONCLUSIONS: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality.
Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells

Tayyeb JZ, Priya M, Guru A, Kishore Kumar MS, Giri J, Garg A, et al.

Mol Biol Rep, 2024 Mar 15;51(1):423.
PMID: 38489102 DOI: 10.1007/s11033-024-09407-7

BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties.
METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity.
RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells.
CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.
Novice driver crashes: The relation between putative causal factors, countermeasures, real world implementations, and policy - A case study in simple, scalable solutions

Fisher DL, Agrawal R, Divekar G, Hamid MA, Krishnan A, Mehranian H, et al.

Accid Anal Prev, 2024 Apr;198:107397.
PMID: 38271896 DOI: 10.1016/j.aap.2023.107397

Novice drivers are at a greatly inflated risk of crashing. This led in the 20th century to numerous attempts to develop training programs that could reduce their crash risk. Yet, none proved effective. Novice drivers were largely considered careless, not clueless. This article is a case study in the United States of how a better understanding of the causes of novice driver crashes led to training countermeasures targeting teen driving behaviors with known associations with crashes. These effects on behaviors were large enough and long-lasting enough to convince insurance companies to develop training programs that they offered around the country to teen drivers. The success of the training programs at reducing the frequency of behaviors linked to crashes also led to several large-scale evaluations of the effect of the training programs on actual crashes. A reduction in crashes was observed. The cumulative effect has now led to state driver licensing agencies considering as a matter of policy both to include items testing the behaviors linked to crashes on licensing exams and to require training on safety critical behaviors. The effort has been ongoing for over a quarter century and is continuing. The case study highlights the critical elements that made it possible to move from a paradigm shift in the understanding of crash causes to the development and evaluation of crash countermeasures, to the implementation of those crash countermeasures, and to subsequent policy changes at the state and federal level. Key among these elements is the development of simple, scalable solutions.
Correction to: Epidemiology and outcomes of open globe injuries: the international globe and adnexal trauma epidemiology study (IGATES)

Hoskin AK, Low R, Sen P, Mishra C, Kamalden TA, Woreta F, et al.

Graefes Arch Clin Exp Ophthalmol, 2021 Sep 08.
PMID: 34495371 DOI: 10.1007/s00417-021-05408-5
Epidemiology and outcomes of open globe injuries: the international globe and adnexal trauma epidemiology study (IGATES)

Hoskin AK, Low R, Sen P, Mishra C, Kamalden TA, Woreta F, et al.

Graefes Arch Clin Exp Ophthalmol, 2021 Jun 26.
PMID: 34173879 DOI: 10.1007/s00417-021-05266-1

PURPOSE: To detail the methodology for a novel ocular trauma registry and utilize the registry to determine the demographics, nature of injury, and associations of severe visual loss for open globe injuries (OGI).
METHODS: Thirteen hospitals in 7 countries used International Globe and Adnexal Trauma Epidemiology Study (IGATES) platform. Patients presenting between April 2009 and 2020 with OGI (with or without) adnexal involvement or intraocular foreign body (IOFB) were included.
RESULTS: Analyses of presenting and final VA, using "severe vision loss" (VA ≤ 6/60) and "no severe loss" (VA > 6/60), were performed. Four hundred fifty-four (64%) patients had VA
Fulltext Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor

Wei GZ, Martin KA, Xing PY, Agrawal R, Whiley L, Wood TK, et al.

Proc Natl Acad Sci U S A, 2021 Jul 06;118(27).
PMID: 34210797 DOI: 10.1073/pnas.2021091118

While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.
The application of clinical registries in ophthalmic trauma-the International Globe and Adnexal Trauma Epidemiology Study (IGATES)

Ng SMS, Low R, Hoskin AK, Rousselot A, Gunasekeran DV, Natarajan S, et al.

Graefes Arch Clin Exp Ophthalmol, 2021 Nov 23.
PMID: 34812939 DOI: 10.1007/s00417-021-05493-6

Ophthalmic trauma is a leading cause of preventable monocular blindness worldwide. The prevalence of ophthalmic trauma varies considerably based on geographic location, socio-economic status, age groups, occupation, and cultural practices such as firework celebrations. Clinical registries are known to be valuable in guiding the diagnosis, management, and prognostication of complex diseases. However, there is currently a lack of a centralized international data repository for ophthalmic trauma. We draw lessons from past and existing clinical registries related to ophthalmology and propose a new suitable international multicenter clinical registry for ophthalmic trauma: the International Globe and Adnexal Trauma Epidemiology Study (IGATES). IGATES is hosted on a secure web-based platform which exhibits user-friendly smart features, an integrated Ocular Trauma Score (OTS) prognosis calculator, efficient data collection points, and schematic graphical software. IGATES currently has 37 participating centers globally. The data collected through IGATES will be primarily used to develop a more robust and improved ophthalmic trauma prognostic classification system, the Ocular Trauma Score-2 (OTS-2), which builds on previous systems such as the Birmingham Eye Trauma Terminology System (BETTS) and Ocular Trauma Score (OTS). Furthermore, IGATES will act as a springboard for further research into the epidemiology, diagnosis, and management of ophthalmic trauma. Ultimately, IGATES serves to advance the field of ophthalmic trauma and improve the care that patients with ophthalmic trauma receive.
Standardization of Nomenclature for Ocular Tuberculosis - Results of Collaborative Ocular Tuberculosis Study (COTS) Workshop

Agrawal R, Agarwal A, Jabs DA, Kee A, Testi I, Mahajan S, et al.

Ocul Immunol Inflamm, 2019 Dec 10.
PMID: 31821096 DOI: 10.1080/09273948.2019.1653933

Purpose: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).Methods: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.Results: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.Conclusion: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity.
The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings

Agrawal R, Testi I, Mahajan S, Yuen YS, Agarwal A, Rousselot A, et al.

Ocul Immunol Inflamm, 2020 Apr 06.
PMID: 32250731 DOI: 10.1080/09273948.2020.1716025

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.