MyMedR

Displaying all 12 publications

Abstract:

Sort:

Modified palatal flap--a simpler approach for removal of palatal tori

Chacko JP, Joseph C

J Oral Maxillofac Surg, 2010 Apr;68(4):943-4.
PMID: 20307780 DOI: 10.1016/j.joms.2009.04.009
Long Term Follow-up of an Open Bicondylar Hoffa Fracture with a Disrupted Extensor Mechanism: A Case Report

Joseph CM, Rama-Prasad YS, Boopalan P, Jepegnanam TS

Malays Orthop J, 2019 Jul;13(2):59-62.
PMID: 31467656 DOI: 10.5704/MOJ.1907.013

This is the first report of a long-term follow-up of an open bicondylar Hoffa with patella fracture. It is interesting to note the radiological changes of osteoarthritis 15 years after global intra-articular injury of the distal femur. The good clinical outcome is possibly due to the integrity of the knee ligaments and reconstruction of the extensor mechanism in addition to stable anatomical reduction and fixation.
Fulltext New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies

Barakat A, Al-Majid AM, Soliman SM, Lotfy G, Ghabbour HA, Fun HK, et al.

Molecules, 2015;20(11):20642-58.
PMID: 26610441 DOI: 10.3390/molecules201119710

The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP) geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity) value of 0.229.
Fulltext A SPION-eicosane protective coating for water soluble capsules: Evidence for on-demand drug release triggered by magnetic hyperthermia

Che Rose L, Bear JC, McNaughter PD, Southern P, Piggott RB, Parkin IP, et al.

Sci Rep, 2016;6:20271.
PMID: 26842884 DOI: 10.1038/srep20271

An orally-administered system for targeted, on-demand drug delivery to the gastrointestinal (GI) tract is highly desirable due to the high instances of diseases of that organ system and harsh mechanical and physical conditions any such system has to endure. To that end, we present an iron oxide nanoparticle/wax composite capsule coating using magnetic hyperthermia as a release trigger. The coating is synthesised using a simple dip-coating process from pharmaceutically approved materials using a gelatin drug capsule as a template. We show that the coating is impervious to chemical conditions within the GI tract and is completely melted within two minutes when exposed to an RF magnetic field under biologically-relevant conditions. The overall simplicity of action, durability and non-toxic and inexpensive nature of our system demonstrated herein are key for successful drug delivery systems.
Fulltext Regulatory agilities impacting review timelines for Pfizer/BioNTech's BNT162b2 mRNA COVID-19 vaccine: a retrospective study

Patel P, Macdonald JC, Boobalan J, Marsden M, Rizzi R, Zenon M, et al.

Front Med (Lausanne), 2023;10:1275817.
PMID: 38020129 DOI: 10.3389/fmed.2023.1275817

The appropriate use of regulatory agilities has the potential to accelerate regulatory review, utilize resources more efficiently and deliver medicines and vaccines more rapidly, all without compromising quality, safety and efficacy. This was clearly demonstrated during the COVID-19 pandemic where regulators and industry rapidly adapted to ensure continued supply of existing critical medicines and review and approve new innovative medicines. In this retrospective study, we analyze the impact of regulatory agilities on the review and approval of Pfizer/BioNTech's BNT162b2 mRNA COVID-19 Vaccine globally using regulatory approval data from 73 country/regional approvals. We report on the critical role of reliance and provide evidence that demonstrates reliance approaches and certain regulatory agilities reduced review times for the COVID-19 vaccine. These findings support the case for more widespread implementation of regulatory agilities and demonstrate the important role of such approaches to improve public health outcomes.
Describing Functioning in People Living With Spinal Cord Injury Across 22 Countries: A Graphical Modeling Approach

Ehrmann C, Reinhardt JD, Joseph C, Hasnan N, Perrouin-Verbe B, Tederko P, et al.

Arch Phys Med Rehabil, 2020 12;101(12):2112-2143.
PMID: 32980339 DOI: 10.1016/j.apmr.2020.09.374

OBJECTIVE: To provide prevalence estimates for problems in functioning of community-dwelling persons with spinal cord injury (SCI) and to examine associations between various areas of functioning with the purpose of supporting countries in identifying targets for interventions.
DESIGN: Cross-sectional survey.
SETTING: Community, 22 countries including all World Health Organization regions.
PARTICIPANTS: Persons (N=12,591) with traumatic or nontraumatic SCI aged 18 years or older.
INTERVENTIONS: Not applicable.
MAIN OUTCOME MEASURES: We estimated the prevalence of problems in 53 areas of functioning from the Brief International Classification of Functioning, Disability and Health (ICF) core set for SCI, long-term context, or ICF rehabilitation set covering 4 domains: impairments in body functions, impairments in mental functions, independence in performing activities, and restrictions in participation. Associations between areas of functioning were identified and visualized using conditional independence graphs.
RESULTS: Participants had a median age of 52 years, 73% were male, and 63% had paraplegia. Feeling tired, bowel dysfunction, sexual functions, spasticity, pain, carrying out daily routine, doing housework, getting up off the floor from lying on the back, pushing open a heavy door, and standing unsupported had the highest prevalence of problems (>70%). Clustering of associations within the 4 functioning domains was found, with the highest numbers of associations within impairments in mental functions. For the whole International Spinal Cord Injury sample, areas with the highest numbers of associations were circulatory problems, transferring bed-wheelchair, and toileting, while for the World Health Organization European and Western Pacific regions, these were dressing upper body, transferring bed-wheelchair, handling stress, feeling downhearted and depressed, and feeling happy.
CONCLUSIONS: In each domain of functioning, high prevalence of problems and high connectivity of areas of functioning were identified. The understanding of problems and the identification of potential targets for intervention can inform decision makers at all levels of the health system aiming to improve the situation of people living with SCI.
Fulltext Are Social Relationships an Underestimated Resource for Mental Health in Persons Experiencing Physical Disability? Observational Evidence From 22 Countries

Fekete C, Tough H, Arora M, Hasnan N, Joseph C, Popa D, et al.

Int J Public Health, 2021;66:619823.
PMID: 34744581 DOI: 10.3389/ijph.2021.619823

Objectives: As advancing evidence on modifiable resources to support mental health in persons experiencing physical disabilities is of particular importance, we investigate whether structural and functional social relationships relate to mental health in people with spinal cord injury (SCI). Methods: Data from 12,330 participants of the International SCI community survey (InSCI) from 22 countries were analyzed. Structural (partnership status, living situation) and functional aspects of social relationships (belongingness, relationship satisfaction, problems with social interactions) were regressed on the SF-36 mental health index (MHI-5), stratified by countries and for the total sample using multilevel models. Results: Functional aspects of social relationships were consistently related to clinically relevant higher MHI-5 scores and lower risk of mental health disorders (MHI-5 >56). Structural social relationships were inconsistently associated with mental health in our sample. Conclusion: This study provides evidence that functional aspects of social relationships are important resources for mental health. Interventions to establish and maintain high quality relationships should be considered in public health interventions and rehabilitation programs to reduce long-term mental health problems in persons experiencing physical disabilities.
Unmet treatment needs of gastroesophageal reflux disease in Asia: gastroesophageal reflux disease in Asia Pacific survey

Goh KL, Choi MG, Hsu WP, Chun HJ, Mahachai V, Kachintorn U, et al.

J Gastroenterol Hepatol, 2014 Dec;29(12):1969-75.
PMID: 24990817 DOI: 10.1111/jgh.12655

Data on patient satisfaction with proton pump inhibitor (PPI) therapy for gastroesophageal reflux disease (GERD) are scarce in Asia. The perspectives of Asian patients with GERD and their satisfaction with PPI therapy were investigated.
Fulltext Clostridia isolated from helminth-colonized humans promote the life cycle of Trichuris species

Sargsian S, Chen Z, Lee SC, Robertson A, Thur RS, Sproch J, et al.

Cell Rep, 2022 Nov 29;41(9):111725.
PMID: 36450245 DOI: 10.1016/j.celrep.2022.111725

Soil-transmitted intestinal worms known as helminths colonize over 1.5 billion people worldwide. Although helminth colonization has been associated with altered composition of the gut microbiota, such as increases in Clostridia, individual species have not been isolated and characterized. Here, we isolate and sequence the genome of 13 Clostridia from the Orang Asli, an indigenous population in Malaysia with a high prevalence of helminth infections. Metagenomic analysis of 650 fecal samples from urban and rural Malaysians confirm the prevalence of species corresponding to these isolates and reveal a specific association between Peptostreptococcaceae family members and helminth colonization. Remarkably, Peptostreptococcaceae isolated from the Orang Asli display superior capacity to promote the life cycle of whipworm species, including hatching of eggs from Trichuris muris and Trichuris trichiura. These findings support a model in which helminths select for gut colonization of microbes that support their life cycle.
Fulltext Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region

Goh KL, Choi MG, Hsu PI, Chun HJ, Mahachai V, Kachintorn U, et al.

J Neurogastroenterol Motil, 2016 Jul 30;22(3):355-66.
PMID: 26932927 DOI: 10.5056/jnm15150

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.
Fulltext Molecular and genomic characterisation of a panel of human anal cancer cell lines

Guerra GR, Kong JC, Millen RM, Read M, Liu DS, Roth S, et al.

Cell Death Dis, 2021 Oct 18;12(11):959.
PMID: 34663790 DOI: 10.1038/s41419-021-04141-5

Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.