Displaying publications 1 - 20 of 78 in total

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  1. Bosch J, Eikelboom JW, Connolly SJ, Bruns NC, Lanius V, Yuan F, et al.
    Can J Cardiol, 2017 08;33(8):1027-1035.
    PMID: 28754388 DOI: 10.1016/j.cjca.2017.06.001
    BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy.

    METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo.

    RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD.

    CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.

  2. Eikelboom JW, Bosch J, Connolly SJ, Tyrwitt J, Fox KAA, Muehlhofer E, et al.
    Eur Heart J Cardiovasc Pharmacother, 2022 Dec 02;8(8):786-795.
    PMID: 35383832 DOI: 10.1093/ehjcvp/pvac023
    AIMS: To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long-term open-label extension (LTOLE).

    METHODS AND RESULTS: Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination.

    CONCLUSION: In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.

  3. CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014 09 26;74(9):3036.
    PMID: 25814912
    Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
  4. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 08 07;74(8):2973.
    PMID: 25814904
    Measurements are reported of the WZ and ZZ production cross sections in proton-proton collisions at [Formula: see text][Formula: see text] in final states where one Z boson decays to b-tagged jets. The other gauge boson, either W or Z, is detected through its leptonic decay (either [Formula: see text], [Formula: see text] or [Formula: see text], [Formula: see text], or [Formula: see text]). The results are based on data corresponding to an integrated luminosity of 18.9 fb[Formula: see text] collected with the CMS detector at the Large Hadron Collider. The measured cross sections, [Formula: see text] and [Formula: see text], are consistent with next-to-leading order quantum chromodynamics calculations.
  5. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 08 20;74(8):3014.
    PMID: 25814909
    The normalised differential top quark-antiquark production cross section is measured as a function of the jet multiplicity in proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] at the LHC with the CMS detector. The measurement is performed in both the dilepton and lepton+jets decay channels using data corresponding to an integrated luminosity of 5.0[Formula: see text]. Using a procedure to associate jets to decay products of the top quarks, the differential cross section of the [Formula: see text] production is determined as a function of the additional jet multiplicity in the lepton+jets channel. Furthermore, the fraction of events with no additional jets is measured in the dilepton channel, as a function of the threshold on the jet transverse momentum. The measurements are compared with predictions from perturbative quantum chromodynamics and no significant deviations are observed.
  6. CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 11 12;74(11):3129.
    PMID: 25814874
    A measurement of differential cross sections for the production of a pair of isolated photons in proton-proton collisions at [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 5.0[Formula: see text] collected with the CMS detector. A data-driven isolation template method is used to extract the prompt diphoton yield. The measured cross section for two isolated photons, with transverse energy above 40 and 25[Formula: see text] respectively, in the pseudorapidity range [Formula: see text], [Formula: see text] and with an angular separation [Formula: see text], is [Formula: see text][Formula: see text]. Differential cross sections are measured as a function of the diphoton invariant mass, the diphoton transverse momentum, the azimuthal angle difference between the two photons, and the cosine of the polar angle in the Collins-Soper reference frame of the diphoton system. The results are compared to theoretical predictions at leading, next-to-leading, and next-to-next-to-leading order in quantum chromodynamics.
  7. CMS Collaboration, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al.
    Eur Phys J C Part Fields, 2014 11 26;74(11):3149.
    PMID: 25814876
    A search for heavy, right-handed neutrinos, [Formula: see text] ([Formula: see text]), and right-handed [Formula: see text] bosons, which arise in the left-right symmetric extensions of the standard model, has been performed by the CMS experiment. The search was based on a sample of two lepton plus two jet events collected in proton-proton collisions at a center-of-mass energy of 8[Formula: see text] corresponding to an integrated luminosity of 19.7 [Formula: see text]. For models with strict left-right symmetry, and assuming only one [Formula: see text] flavor contributes significantly to the [Formula: see text] decay width, the region in the two-dimensional [Formula: see text] mass plane excluded at a 95 % confidence level extends to approximately [Formula: see text] and covers a large range of neutrino masses below the [Formula: see text] boson mass, depending on the value of [Formula: see text]. This search significantly extends the [Formula: see text] exclusion region beyond previous results.
  8. Schaefer N, Rotermund C, Blumrich EM, Lourenco MV, Joshi P, Hegemann RU, et al.
    J Neurochem, 2017 Jun 20.
    PMID: 28632905 DOI: 10.1111/jnc.14107
    One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation and long-term depression, respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by long-term potentiation and long-term depression, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity. Read the Editorial Highlight for this article on doi: 10.1111/jnc.14102.
  9. Amiri H, Aghbashlo M, Sharma M, Gaffey J, Manning L, Moosavi Basri SM, et al.
    Nat Food, 2022 Oct;3(10):822-828.
    PMID: 37117878 DOI: 10.1038/s43016-022-00591-y
    Crustacean waste, consisting of shells and other inedible fractions, represents an underutilized source of chitin. Here, we explore developments in the field of crustacean-waste-derived chitin and chitosan extraction and utilization, evaluating emerging food systems and biotechnological applications associated with this globally abundant waste stream. We consider how improving the efficiency and selectivity of chitin separation from wastes, redesigning its chemical structure to improve biotechnology-derived chitosan, converting it into value-added chemicals, and developing new applications for chitin (such as the fabrication of advanced nanomaterials used in fully biobased electric devices) can contribute towards the United Nations Sustainable Development Goals. Finally, we consider how gaps in the research could be filled and future opportunities could be developed to make optimal use of this important waste stream for food systems and beyond.
  10. Ge N, Brugge WR, Saxena P, Sahai A, Adler DG, Giovannini M, et al.
    Endosc Ultrasound, 2019 9 26;8(6):418-427.
    PMID: 31552915 DOI: 10.4103/eus.eus_61_19
    Background and Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field.

    Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized.

    Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year.

    Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

  11. Syed NH, Zunaina E, Wan-Nazatul Shima S, Sharma M, Shatriah I
    Korean J Ophthalmol, 2022 Oct;36(5):452-462.
    PMID: 35989077 DOI: 10.3341/kjo.2022.0010
    MicroRNAs (miRNAs) are the small noncoding RNA molecules which regulate target gene expression posttranscriptionally. They are known to regulate key cellular processes like inflammation, cell differentiation, cell proliferation, and cell apoptosis across various ocular diseases. Due to their easier access, recent focus has been laid on the investigation of miRNA expression and their involvement in several conjunctival diseases. The aim of this narrative review is to provide understanding of the miRNAs and describe the current role of miRNAs as the mediators of the various conjunctival diseases. A literature search was made using PubMed, Scopus, and Web of Science databases for studies involving miRNAs in the conjunctival pathological conditions. Original articles in the last 10 years involving both human and animal models were included. Literature search retrieved 27 studies matching our criteria. Pertaining to the numerous literatures, there is a strong correlation between miRNA and the various pathological conditions that occur in the conjunctiva. miRNAs are involved in various physiological processes such as cell differentiation, proliferation, apoptosis, development, and inflammation by regulating various signaling pathways, genes, proteins, and mediators. Pterygium was the most studied conjunctival disease for miRNA involvement, whereas miRNA research in allergic conjunctivitis is still in its early stages. Our review provides deep insights into the various miRNAs playing an important role in the various conjunctival diseases. miRNAs do have the potential to serve as noninvasive biomarkers with diagnostic, prognostic, and therapeutic implications. However, multitudinous studies are required to validate miRNAs as the reliable biomarkers in conjunctival pathologies and its targeted therapy.
  12. Ching TY, Quar TK, Johnson EE, Newall P, Sharma M
    J Am Acad Audiol, 2015 Mar;26(3):260-74.
    PMID: 25751694 DOI: 10.3766/jaaa.26.3.6
    BACKGROUND: An important goal of providing amplification to children with hearing loss is to ensure that hearing aids are adjusted to match targets of prescriptive procedures as closely as possible. The Desired Sensation Level (DSL) v5 and the National Acoustic Laboratories' prescription for nonlinear hearing aids, version 1 (NAL-NL1) procedures are widely used in fitting hearing aids to children. Little is known about hearing aid fitting outcomes for children with severe or profound hearing loss.

    PURPOSE: The purpose of this study was to investigate the prescribed and measured gain of hearing aids fit according to the NAL-NL1 and the DSL v5 procedure for children with moderately severe to profound hearing loss; and to examine the impact of choice of prescription on predicted speech intelligibility and loudness.

    RESEARCH DESIGN: Participants were fit with Phonak Naida V SP hearing aids according to the NAL-NL1 and DSL v5 procedures. The Speech Intelligibility Index (SII) and estimated loudness were calculated using published models.

    STUDY SAMPLE: The sample consisted of 16 children (30 ears) aged between 7 and 17 yr old.

    DATA COLLECTION AND ANALYSIS: The measured hearing aid gains were compared with the prescribed gains at 50 (low), 65 (medium), and 80 dB SPL (high) input levels. The goodness of fit-to-targets was quantified by calculating the average root-mean-square (RMS) error of the measured gain compared with prescriptive gain targets for 0.5, 1, 2, and 4 kHz. The significance of difference between prescriptions for hearing aid gains, SII, and loudness was examined by performing analyses of variance. Correlation analyses were used to examine the relationship between measures.

    RESULTS: The DSL v5 prescribed significantly higher overall gain than the NAL-NL1 procedure for the same audiograms. For low and medium input levels, the hearing aids of all children fit with NAL-NL1 were within 5 dB RMS of prescribed targets, but 33% (10 ears) deviated from the DSL v5 targets by more than 5 dB RMS on average. For high input level, the hearing aid fittings of 60% and 43% of ears deviated by more than 5 dB RMS from targets of NAL-NL1 and DSL v5, respectively. Greater deviations from targets were associated with more severe hearing loss. On average, the SII was higher for DSL v5 than for NAL-NL1 at low input level. No significant difference in SII was found between prescriptions at medium or high input level, despite greater loudness for DSL v5 than for NAL-NL1.

    CONCLUSIONS: Although targets between 0.25 and 2 kHz were well matched for both prescriptions in commercial hearing aids, gain targets at 4 kHz were matched for NAL-NL1 only. Although the two prescriptions differ markedly in estimated loudness, they resulted in comparable predicted speech intelligibility for medium and high input levels.

  13. Suthar SK, Boon HL, Sharma M
    Eur J Med Chem, 2014 Mar 3;74:135-44.
    PMID: 24457265 DOI: 10.1016/j.ejmech.2013.12.052
    The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22β-hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 μmol, respectively against TNF-α induced activation of NF-κB. The congeners 12 and 13 exhibited inhibition of IKKβ in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 μmol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties.
  14. Quar TK, Ching TY, Newall P, Sharma M
    Int J Audiol, 2013 May;52(5):322-32.
    PMID: 23570290 DOI: 10.3109/14992027.2012.755740
    The study aims to compare the performance of hearing aids fitted according to the NAL-NL1 and DSL v5 prescriptive procedure for children.
  15. Monika, Sharma A, Suthar SK, Aggarwal V, Lee HB, Sharma M
    Bioorg Med Chem Lett, 2014 Aug 15;24(16):3814-8.
    PMID: 25027934 DOI: 10.1016/j.bmcl.2014.06.068
    The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.
  16. Kaur A, Dhiman S, Lee HB, Sharma M
    Anticancer Agents Med Chem, 2022;22(18):3182-3192.
    PMID: 35469577 DOI: 10.2174/1871520622666220425114553
    BACKGROUND: Camptothecin is a naturally occurring alkaloid obtained from the stem wood of the Chinese tree, Camptotheca acuminata. It exerts pharmacological effects due to its ability to selectively inhibit the type-I topoisomerase DNA nuclear enzyme. Several semisynthetic analogs of camptothecin have been synthesized to date possessing antitumor activity.

    OBJECTIVE: Camptothecin (CPT) is one of the most promising anticancer drugs but it produces various side effects because of its non-selectivity towards cancer cells. To overcome these adverse effects, we synthesized biotin conjugate of camptothecin, which was linked via a self-immolative disulfide linker (CPT-SS-Biotin).

    METHODS: Biotin conjugated camptothecin linked through a disulfide bond was synthesized following schemes, and the structural characterization was carried out. The stability and drug release studies were performed in the presence of glutathione (GSH) while in vitro studies were performed on 4T1 tumor cell lines. In vivo pharmacological investigation was done using an antitumor Wistar rat model.

    RESULTS: The stability and drug release studies were performed in the presence of glutathione (GSH), and CPT-SSBiotin was found to be physiologically stable moiety and can only be cleaved in the presence of GSH to release free CPT. The CPT-SS-Biotin showed higher toxicity in the biotin-overexpressing 4T1 tumor cell line with a lower IC50 value (8.44 μM) compared to camptothecin alone (IC50 > 30 μM). CPT-SS-Biotin also showed 10.6% higher cellular uptake by cells in comparison to free camptothecin. The CPT-SS-Biotin was delivered to cells by binding to the biotin receptors on the cell surface, followed by energy-dependent endocytosis and internalization to cause cellular toxicity.

    CONCLUSION: In-vivo tumor suppression studies and in vitro cell line studies along with serological parameters and histopathological studies showed that conjugate produced a high therapeutic effect and remarkably reduced toxic effects in comparison to free CPT. The results suggested that biotinylation of camptothecin via disulfide linker can be a safe and efficacious method in cancer therapeutics.

  17. Ray P, Sharma J, Marak RS, Singhi S, Taneja N, Garg RK, et al.
    Indian J Med Res, 2004 Dec;120(6):523-6.
    PMID: 15654137
    Though Chromobacterium violaceum is a common inhabitant of soil and water in tropical and sub-tropical regions, human infections are rare but when they do occur result in high mortality. Since the first case from Malaysia in 1927, about 150 cases have been reported in world literature. Till date 6 cases have been reported from southern and eastern parts of India. We report here a case of C. violaceum septicaemia, probably the first case from north India. The patient, a 6 and a half year old boy was admitted with high fever. The patient had anaemia, neutrophilic leucocytosis and bilateral chest infiltrates. Routine and bacteriological investigations were carried out to establish the aetiological diagnosis. C. violaceum was isolated in pure culture from blood and pus. The patient was successfully treated with ciprofloxacin and amikacin. This is probably the first documented case report of C. violaceum infection from north India and the only Indian case with septicaemia which survived.
  18. Pannu D, Bharti R, Anand HP, Sharma M
    Malays J Med Sci, 2016 Sep;23(5):96-99.
    PMID: 27904431
    Term, live abdominal pregnancy secondary to rupture of a uterine rudimentary horn is a rare condition. Pregnancies conceived in the rudimentary horn of the uterus usually rupture during early gestation and present as a catastrophic event. However, rarely, after rupture of the uterine horn the foetus may continue to grow in the abdominal cavity and reach term gestation. A primigravida with a term pregnancy was referred to our centre for caesarean section with ultrasonography findings of transverse lie and placenta previa. During surgery, a live baby was extracted from the abdominal cavity, revealing a bicornuate uterus with rupture of the rudimentary horn. The early peroperative diagnosis and prompt control of the bleeding with excision of the rudimentary horn and transfusion of multiple blood products saved the patient's life. The case is presented for its rarity and to highlight the importance of a high index of suspicion in cases presenting with abnormal foetal presentation.
  19. Chen DS, Hamoudi W, Mustapha B, Layden J, Nersesov A, Reic T, et al.
    J Viral Hepat, 2017 10;24 Suppl 2:44-63.
    PMID: 29105286 DOI: 10.1111/jvh.12759
    The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.
  20. Sharma M, Prasher P, Mehta M, Zacconi FC, Singh Y, Kapoor DN, et al.
    Drug Dev Res, 2020 Jul 30.
    PMID: 32729640 DOI: 10.1002/ddr.21724
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