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1.
JMIR Perioper Med ; 5(1): e35997, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35763332

ABSTRACT

BACKGROUND: Postoperative care is influenced by various factors such as compliance, comprehension, retention of instructions, and other unaccounted elements. It is imperative that patients adhere to the instructions and prescribed regimen for smooth and placid healing. ExoDont, an Android-based mobile health app, was designed to ensure a smooth postoperative period for patients after a dental extraction. Besides providing postoperative instructions at defined intervals, the app also sends drug reminders as an added advantage over other available, conventional methods. OBJECTIVE: The aim of this study was to compare the compliance rate of individuals with respect to the prescribed regimen and postoperative instructions. Additionally, we aimed to assess any changes in the postoperative complication rate of patients assigned to 3 categories: the verbal, verbal plus written, and ExoDont app-based delivery groups. METHODS: We conducted a pilot, nonrandomized, and prospective comparative study in which patients after tooth extraction were assigned to 3 groups-verbal (Group A), verbal plus written (Group B), and ExoDont app-based delivery (Group C)-based on the eligibility criteria, and a 1-week follow-up was planned to obtain the responses regarding compliance and postoperative complications from the participants. RESULTS: In total, 90 patients were recruited and equally divided into 3 groups. Compliance to prescribed drug was found to be the highest in Group C, where of the 30 participants, 25 (83%) and 28 (93%) followed the entire course of antibiotics and analgesics, respectively. For postoperative instructions, higher compliance was observed in Group C in relation to compliance to diet restrictions (P=.001), not rinsing for 24 hours (P<.001), and warm saline rinses after 24 hours (P=.001). However, the difference was not significant for smoking restrictions (P=.07) and avoiding alcohol (P=.16). Moreover, the difference in postoperative complication rate was not statistically significant among the 3 groups (P=.31). CONCLUSIONS: As evident from the results, it is anticipated that the ExoDont app will be helpful in circumventing the unaccounted possibilities of missing the prescribed dosage and postoperative instructions and ensuring the smooth recovery of patients after dental extraction. However, future studies are required to establish this app-based method of delivery of postoperative instructions as a viable option in routine clinical practice.

2.
iScience ; 24(6): 102414, 2021 Jun 25.
Article in English | MEDLINE | ID: mdl-34041454

ABSTRACT

Sex-hormone-binding globulin (SHBG) regulates the transport and bioavailability of estradiol. The dynamics of estradiol's binding to SHBG are incompletely understood, although it is believed that estradiol binds to each monomer of SHBG dimer with identical affinity (Kd ∼2 nM). Contrary to the prevalent view, we show that estradiol's binding to SHBG is nonlinear, and the "apparent" Kd changes with varying estradiol and SHBG concentrations. Estradiol's binding to each SHBG monomer influences residues in the ligand-binding pocket of both monomers and differentially alters the conformational and energy landscapes of both monomers. Monomers are not energetically or conformationally equivalent even in fully bound state. Estradiol's binding to SHBG involves bidirectional, inter-monomeric allostery that changes the distribution of both monomers among various energy and conformational states. Inter-monomeric allostery offers a mechanism to extend the binding range of SHBG and regulate hormone bioavailability as estradiol concentrations vary widely during life.

3.
Front Dent ; 18: 40, 2021.
Article in English | MEDLINE | ID: mdl-35965732

ABSTRACT

The choice of an appropriate autogenous source of stem cells has not been adequately addressed especially for intraoral bone regeneration. The current review aims to assess the clinical success of various human stem cells in oral bone regeneration. Articles studying the potential of various stem cells utilized for reconstruction of intraoral bone defects in humans were included in this review. Relevant articles were electronically searched in MEDLINE-PubMed database using keywords with different combinations. Only the articles published in English between 2006 and 2020 were included in this review. It was concluded that intra and extraoral stem cells can be successfully used for bone regeneration of various jaw defects. Depending on the origin, quantity, and quality, each cell type has its own advantages and disadvantages. Also, it brings to the fore the need for more clinical studies to validate and adopt the use of stem cells in regular clinical practice.

4.
JMIR Perioper Med ; 4(2): e31852, 2021 Dec 31.
Article in English | MEDLINE | ID: mdl-34982720

ABSTRACT

BACKGROUND: The postoperative period is crucial for the initiation of healing and prevention of complications after any surgical procedure. Due to factors such as poor compliance, comprehension, and retention of instructions, and other unaccounted factors, the objectives of postoperative care are not always achieved. Therefore, an Android-based mobile health app (ExoDont) was developed to ensure a smooth postoperative period for patients after a dental extraction. The ExoDont app delivers reminders for postoperative instructions and drug intake at defined intervals, thus fostering self-reliance among patients in taking their prescribed dose of medication. OBJECTIVE: The aim of this study is to design, develop, and validate ExoDont, an innovative app for improved adherence to postoperative instructions after tooth extraction. METHODS: A postoperative treatment protocol was developed by a team of oral and maxillofacial surgeons and general dentists, following which the clinical and technological requirements of the app were determined along with the software engineers, graphic designers, and applications architect in the team. ExoDont was developed to provide timely reminders for medication and postoperative care. The app was field tested and validated using the User Version of the Mobile Application Rating Scale. RESULTS: The ExoDont software design was divided into a 3-level architecture comprising a user interface application, logical layer, and database layer. The software architecture consists of an Android-based ExoDont app for patients and a web version of the admin panel. The testing and validation of the ExoDont app revealed that Perceived Impact received the highest mean score of all rated components (mean 4.6, SD 0.5), while Engagement received the lowest mean score (mean 3.5, SD 0.8). CONCLUSIONS: The testing and validation of the app support its usability and functionality, as well as its impact on users. The ExoDont app has been designed, keeping the welfare of patients in view, in a user-friendly manner that will help patients adhere to the prescribed drug regimen and ensure easy and efficient dissemination of postoperative instructions. It could play an instrumental role in fostering compliance among patients and significantly decrease the complication rate following dental extractions.

5.
Endocrinology ; 162(2)2021 02 01.
Article in English | MEDLINE | ID: mdl-33125473

ABSTRACT

Human serum albumin (HSA) acts as a carrier for testosterone, other sex hormones, fatty acids, and drugs. However, the dynamics of testosterone's binding to HSA and the structure of its binding sites remain incompletely understood. Here, we characterize the dynamics of testosterone's binding to HSA and the stoichiometry and structural location of the binding sites using 2-dimensional nuclear magnetic resonance (2D NMR), fluorescence spectroscopy, 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt partitioning, and equilibrium dialysis, complemented by molecular modeling. 2D NMR studies showed that testosterone competitively displaced 18-[13C]-oleic acid from at least 3 known fatty acid binding sites on HSA that also bind many drugs. Binding isotherms of testosterone's binding to HSA generated using fluorescence spectroscopy and equilibrium dialysis were nonlinear and the apparent dissociation constant varied with different concentrations of testosterone and HSA. The binding isotherms neither conformed to a linear binding model with 1:1 stoichiometry nor to 2 independent binding sites; the binding isotherms were most consistent with 2 or more allosterically coupled binding sites. Molecular dynamics studies revealed that testosterone's binding to fatty acid binding site 3 on HSA was associated with conformational changes at site 6, indicating that residues in in these 2 distinct binding sites are allosterically coupled. There are multiple, allosterically coupled binding sites for testosterone on HSA. Testosterone shares these binding sites on HSA with free fatty acids, which could displace testosterone from HSA under various physiological states or disease conditions, affecting its bioavailability.


Subject(s)
Serum Albumin, Human/metabolism , Testosterone/metabolism , Carbon Isotopes , Magnetic Resonance Spectroscopy , Molecular Dynamics Simulation , Spectrometry, Fluorescence
6.
Matrix Biol ; 65: 45-58, 2018 01.
Article in English | MEDLINE | ID: mdl-28789925

ABSTRACT

Thrombospondin-2 (TSP2) is a potent inhibitor of angiogenesis whose expression is dynamically regulated following injury. In the present study, it is shown that HIF-1α represses TSP2 transcription. Specifically, in vitro studies demonstrate that the prolyl hydroxylase inhibitor DMOG or hypoxia decrease TSP2 expression in fibroblasts. This effect is shown to be via a transcriptional mechanism as hypoxia does not alter TSP2 mRNA stability and this effect requires the TSP2 promoter. In addition, the documented repressive effect of nitric oxide (NO) on TSP2 is shown to be non-canonical and involves stabilization of hypoxia inducible factor-1a (HIF-1α). The regulation of TSP2 by hypoxia is supported by the in vivo observation that TSP2 has spatiotemporal expression distinct from regions of hypoxia in gastrocnemius muscle following murine hindlimb ischemia (HLI). A role for TSP2 regulation by HIF-1α is supported by the dysregulation of TSP2 expression in SM22α-cre HIF-1α KO mice following HLI. Indeed, there is a reduction in blood flow recovery in the SM22a-cre HIF-1α KO mice compared to littermate controls following HLI surgery, associated with impaired recovery and increased TSP2 levels. Moreover, SM22α-cre HIF-1α KO smooth muscle cells mice have increased TSP2 mRNA levels that persist in hypoxia. These findings identify a novel, ischemia-induced pro-angiogenic mechanism involving the transcriptional repression of TSP2 by HIF-1α.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Thrombospondins/genetics , Thrombospondins/metabolism , Transcription, Genetic , Amino Acids, Dicarboxylic/pharmacology , Animals , Cell Hypoxia , HEK293 Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice , Muscle, Skeletal/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , NIH 3T3 Cells , Promoter Regions, Genetic
7.
Endocr Rev ; 38(4): 302-324, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28673039

ABSTRACT

In the circulation, testosterone and other sex hormones are bound to binding proteins, which play an important role in regulating their transport, distribution, metabolism, and biological activity. According to the free hormone hypothesis, which has been debated extensively, only the unbound or free fraction is biologically active in target tissues. Consequently, accurate determination of the partitioning of testosterone between bound and free fractions is central to our understanding of how its delivery to the target tissues and biological activity are regulated and consequently to the diagnosis and treatment of androgen disorders in men and women. Here, we present a historical perspective on the evolution of our understanding of the binding of testosterone to circulating binding proteins. On the basis of an appraisal of the literature as well as experimental data, we show that the assumptions of stoichiometry, binding dynamics, and the affinity of the prevailing models of testosterone binding to sex hormone-binding globulin and human serum albumin are not supported by published experimental data and are most likely inaccurate. This review offers some guiding principles for the application of free testosterone measurements in the diagnosis and treatment of patients with androgen disorders. The growing number of testosterone prescriptions and widely recognized problems with the direct measurement as well as the computation of free testosterone concentrations render this critical review timely and clinically relevant.


Subject(s)
Serum Albumin, Human/metabolism , Sex Hormone-Binding Globulin/metabolism , Testosterone/metabolism , Transcortin/metabolism , Humans , Testosterone/analysis
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