Browse publications by year: 2019

  1. Anwar A, Mungroo MR, Anwar A, Sullivan WJ, Khan NA, Siddiqui R
    ACS Infect Dis, 2019 Dec 13;5(12):2039-2046.
    PMID: 31612700 DOI: 10.1021/acsinfecdis.9b00263
    Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiamoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet-visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size distribution with the average diameter of around 100 nm. Guanabenz and its noble metal nanoconjugates exhibited potent antiamoebic effects in the range of 2.5 to 100 μM against both amoebae. Nanoparticle conjugation enhanced the antiamoebic effects of guanabenz, as more potent activity was observed at a lower effective concentration (2.5 and 5 μM) compared to the drug alone. Moreover, encystation and excystation assays revealed that guanabenz inhibits the interconversion between the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were also observed. Notably, pretreatment of A. castellanii with guanabenz and its nanoconjugates exhibited a significant reduction in the host cell cytopathogenicity from 65% to 38% and 2% in case of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic evaluation of guanabenz and its nanoconjugates revealed negligible cytotoxicity against human cells. Guanabenz is already approved for hypertension and crosses the blood-brain barrier; the results of our current study suggest that guanabenz and its conjugated gold and silver nanoparticles can be repurposed as a potential drug for treating brain-eating amoebic infections.
    MeSH terms: Amebicides/pharmacology; Amebicides/chemistry; Cell Line; Gold/chemistry*; Guanabenz/pharmacology*; Guanabenz/chemistry; HeLa Cells; Humans; Particle Size; Silver/chemistry*; Molecular Structure; Naegleria fowleri/drug effects*; Naegleria fowleri/growth & development; Microscopy, Atomic Force; Acanthamoeba castellanii/drug effects*; Acanthamoeba castellanii/growth & development; Trophozoites/drug effects; Metal Nanoparticles; Drug Repositioning; Nanoconjugates/chemistry
  2. Loo JMY, Kraus SW, Potenza MN
    J Behav Addict, 2019 Dec 01;8(4):625-648.
    PMID: 31830810 DOI: 10.1556/2006.8.2019.64
    BACKGROUND AND AIMS: This systematic review analyzes and summarizes gambling-related findings from the nationally representative US National Epidemiological Survey on Alcohol and Related Conditions (NESARC) data.

    METHODS: Systematic literature searches in accordance with PRISMA guidelines found 51 eligible studies that met inclusion criteria. Eight studies utilized both Waves 1 and 2 NESARC data, and selection of sample sizes varied from 185 to 43,093 individuals, consistent with specified research objectives of each study.

    RESULTS: The prevalence of lifetime pathological gambling was 0.42% (0.64% among men, 0.23% among women), while past-year prevalence was 0.16%. Pathological gambling rates were generally higher in populations with substance-use disorders and other psychiatric diagnoses. Rates of adverse childhood experiences and suicidal attempts were higher among individuals with problem or pathological gambling. Early-onset gamblers were more likely to be male, be never married, have incomes below $70,000, belong to younger cohorts and have Cluster B personality disorders, but less likely to be diagnosed with mood disorders. While pathological gambling was related to obesity, increased stress, and poorer physical health among general age groups, recreational gambling was linked with improved physical and mental functioning in older adults.

    CONCLUSIONS: The NESARC has provided important information on the correlates of pathological gambling and subdiagnostic patterns of gambling behaviors. Additional studies should examine these relationships in the current gambling environment and longitudinally with aims of implementing policies to improve the public health.

    MeSH terms: Gambling/epidemiology*; Health Surveys; Humans; Longitudinal Studies; United States/epidemiology
  3. Chew KS, Ahmad Razali S, Wong SSL, Azizul A, Ismail NF, Robert SJKCA, et al.
    Int J Emerg Med, 2019 Dec 12;12(1):40.
    PMID: 31830912 DOI: 10.1186/s12245-019-0256-5
    BACKGROUND: The influence of past familial experiences of receiving cardiopulmonary resuscitation (CPR) and medical help in various cardiac arrest and nonfatal cardiac events toward willingness to "pay it forward" by helping the next cardiac arrest victim was explored.

    METHODS: Using a validated questionnaire, 6248 participants were asked to rate their willingness to perform bystander chest compression with mouth-to-mouth ventilation and chest compression-only CPR. Their past familial experiences of receiving cardiopulmonary resuscitation (CPR) and medical help in various cardiac arrest and nonfatal cardiac events were also recorded.

    RESULTS: Kruskal-Wallis test with post hoc Dunn's pairwise comparisons showed that the following were significantly more willing to perform CPR with mouth-to-mouth ventilation: familial experience of "nonfatal cardiac events" (mean rank = 447) vs "out-of-hospital cardiac arrest with no CPR" (mean rank = 177), U = 35442.5, z = -2.055, p = 0.04; "in-hospital cardiac arrest and successful CPR" (mean rank = 2955.79) vs "none of these experiences" (mean rank = 2468.38), U = 111903, z = -2.60, p = 0.01; and "in-hospital cardiac arrest with successful CPR" (mean rank = 133.45) vs "out-of-hospital arrest with no CPR" (mean rank = 112.36), U = 4135.5, z = -2.06, p = 0.04. For compression-only CPR, Kruskal-Wallis test with multiple runs of Mann-Whitney U tests showed that "nonfatal cardiac events" group was statistically higher than the group with "none of these experiences" (mean rank = 3061.43 vs 2859.91), U = 1194658, z = -2.588, p = 0.01. The groups of "in-hospital cardiac arrest with successful CPR" and "in-hospital cardiac arrest with transient return of spontaneous circulation" were the most willing groups to perform compression-only CPR.

    CONCLUSION: Prior familial experiences of receiving CPR and medical help, particularly among those with successful outcomes in a hospital setting, seem to increase the willingness to perform bystander CPR.

    MeSH terms: Humans; Mouth; Surveys and Questionnaires; Cardiopulmonary Resuscitation; Statistics, Nonparametric; Out-of-Hospital Cardiac Arrest
  4. Kamarudin MNA, Sarker MMR, Zhou JR, Parhar I
    J Exp Clin Cancer Res, 2019 Dec 12;38(1):491.
    PMID: 31831021 DOI: 10.1186/s13046-019-1495-2
    Growing evidence showed the increased prevalence of cancer incidents, particularly colorectal cancer, among type 2 diabetic mellitus patients. Antidiabetic medications such as, insulin, sulfonylureas, dipeptyl peptidase (DPP) 4 inhibitors and glucose-dependent insulinotropic peptide (GLP-1) analogues increased the additional risk of different cancers to diabetic patients. Conversely, metformin has drawn attention among physicians and researchers since its use as antidiabetic drug exhibited beneficial effect in the prevention and treatment of cancer in diabetic patients as well as an independent anticancer drug. This review aims to provide the comprehensive information on the use of metformin at preclinical and clinical stages among colorectal cancer patients. We highlight the efficacy of metformin as an anti-proliferative, chemopreventive, apoptosis inducing agent, adjuvant, and radio-chemosensitizer in various colorectal cancer models. This multifarious effects of metformin is largely attributed to its capability in modulating upstream and downstream molecular targets involved in apoptosis, autophagy, cell cycle, oxidative stress, inflammation, metabolic homeostasis, and epigenetic regulation. Moreover, the review highlights metformin intake and colorectal cancer risk based on different clinical and epidemiologic results from different gender and specific population background among diabetic and non-diabetic patients. The improved understanding of metformin as a potential chemotherapeutic drug or as neo-adjuvant will provide better information for it to be used globally as an affordable, well-tolerated, and effective anticancer agent for colorectal cancer.
    MeSH terms: Animals; Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use*; Cell Survival/drug effects; Clinical Trials as Topic; Humans; Metformin/pharmacology; Metformin/therapeutic use*; Colorectal Neoplasms/drug therapy*; Cell Proliferation/drug effects
  5. Garza-Manero S, Sindi AAA, Mohan G, Rehbini O, Jeantet VHM, Bailo M, et al.
    Epigenetics Chromatin, 2019 12 12;12(1):73.
    PMID: 31831052 DOI: 10.1186/s13072-019-0320-7
    BACKGROUND: Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells.

    RESULTS: We show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers Nanog and Ssea1, and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at the Nanog and Oct4 loci. At endodermal/mesodermal genes, Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2.

    CONCLUSIONS: We conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers.

    MeSH terms: Cell Self Renewal; Animals; Cell Differentiation; Chromatin/metabolism*; Histones/metabolism; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/chemistry; Neurons/cytology; Neurons/metabolism; Protein Processing, Post-Translational; HMGN1 Protein/genetics; HMGN1 Protein/metabolism; HMGN2 Protein/genetics; HMGN2 Protein/metabolism*; Pluripotent Stem Cells/cytology; Pluripotent Stem Cells/metabolism; Cell Line, Tumor; Octamer Transcription Factor-3/metabolism; Mice; Basic Helix-Loop-Helix Transcription Factors/metabolism; Basic Helix-Loop-Helix Transcription Factors/chemistry; Neural Stem Cells/cytology; Neural Stem Cells/metabolism; Nanog Homeobox Protein/genetics; Nanog Homeobox Protein/metabolism
  6. Ma B, Khazali A, Shao H, Jiang Y, Wells A
    Cell Commun Signal, 2019 12 12;17(1):164.
    PMID: 31831069 DOI: 10.1186/s12964-019-0489-1
    BACKGROUND: Carcinoma cells shift between epithelial and mesenchymal phenotypes during cancer progression, as defined by surface presentation of the cell-cell cohesion molecule E-cadherin, affecting dissemination, progression and therapy responsiveness. Concomitant with the loss of E-cadherin during the mesenchymal transition, the predominant receptor isoform for ELR-negative CXC ligands shifts from CXCR3-B to CXCR3-A which turns this classical G-protein coupled receptor from an inhibitor to an activator of cell migration, thus promoting tumor cell invasiveness. We proposed that CXCR3 was not just a coordinately changed receptor but actually a regulator of the cell phenotype.

    METHODS: Immunoblotting, immunofluorescence, quantitative real-time PCR and flow cytometry assays investigated the expression of E-cadherin and CXCR3 isoforms. Intrasplenic inoculation of human prostate cancer (PCa) cells with spontaneous metastasis to the liver analyzed E-cadherin and CXCR3-B expression during cancer progression in vivo.

    RESULTS: We found reciprocal regulation of E-cadherin and CXCR3 isoforms. E-cadherin surface expression promoted CXCR3-B presentation on the cell membrane, and to a lesser extent increased its mRNA and total protein levels. In turn, forced expression of CXCR3-A reduced E-cadherin expression level, whereas CXCR3-B increased E-cadherin in PCa. Meanwhile, a positive correlation of E-cadherin and CXCR3-B expression was found both in experimental PCa liver micro-metastases and patients' tissue.

    CONCLUSIONS: CXCR3-B and E-cadherin positively correlated in vitro and in vivo in PCa cells and liver metastases, whereas CXCR3-A negatively regulated E-cadherin expression. These results suggest that CXCR3 isoforms may play important roles in cancer progression and dissemination via diametrically regulating tumor's phenotype.

    MeSH terms: Animals; Humans; Male; Neoplasms, Experimental/genetics; Neoplasms, Experimental/metabolism; Neoplasms, Experimental/pathology; Phenotype; Prostatic Neoplasms/genetics*; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology; Tumor Cells, Cultured; Signal Transduction/genetics; Down-Regulation; Cadherins/genetics*; Cadherins/metabolism; Mice, SCID; Mice, Inbred NOD; Protein Isoforms; Mice; Receptors, CXCR3/genetics*; Receptors, CXCR3/metabolism
  7. Wong EHC, Chong AW
    Am J Otolaryngol, 2019 12 05;41(2):102367.
    PMID: 31831185 DOI: 10.1016/j.amjoto.2019.102367
    BACKGROUND: Many studies have looked at the effect of functional endoscopic sinus surgeries (FESS) on nasalance, nasal consonant and nasalized vowels. Only two studies investigated the effect of FESS on vocal sound quality and have not found statistically significant changes before and after operations. The aim of this study was to examine the short-term and long-term objective and subjective changes in the vocal quality of patients after FESS, comparing patients with and without nasal polyps.

    METHODS: Sixteen patients were recruited for voice analysis during pre-operative, within two weeks and at least three months post-operatively. Subjective questionnaire was used to assess perception of voice changes.

    RESULTS: There were no statistically significant changes in the acoustic parameters of patients with nasal polyposis. In patients with CRS without polyps, there was a statistically significant increase in fundamental frequency (F0) in nasal sound during early follow up. The changes in soft phonation index (SPI) values between the two groups were statistically significant during early follow-ups. Only patients with nasal polyposis perceived a subjective change in their voice post-operatively.

    CONCLUSIONS: Clinicians should inform all patients, especially voice professionals about the possible effects of endoscopic sinus surgeries on their voice quality.

    MeSH terms: Endoscopy/adverse effects*; Endoscopy/methods*; Humans; Nasal Polyps*; Paranasal Sinuses/surgery*; Voice/physiology*
  8. Díaz S, Settele J, Brondízio ES, Ngo HT, Agard J, Arneth A, et al.
    Science, 2019 12 13;366(6471).
    PMID: 31831642 DOI: 10.1126/science.aax3100
    The human impact on life on Earth has increased sharply since the 1970s, driven by the demands of a growing population with rising average per capita income. Nature is currently supplying more materials than ever before, but this has come at the high cost of unprecedented global declines in the extent and integrity of ecosystems, distinctness of local ecological communities, abundance and number of wild species, and the number of local domesticated varieties. Such changes reduce vital benefits that people receive from nature and threaten the quality of life of future generations. Both the benefits of an expanding economy and the costs of reducing nature's benefits are unequally distributed. The fabric of life on which we all depend-nature and its contributions to people-is unravelling rapidly. Despite the severity of the threats and lack of enough progress in tackling them to date, opportunities exist to change future trajectories through transformative action. Such action must begin immediately, however, and address the root economic, social, and technological causes of nature's deterioration.
    MeSH terms: Conservation of Natural Resources*; Humans; Human Activities/trends*; Population Growth; Quality of Life*; Earth (Planet)
  9. Baby R, Saifullah B, Hussein MZ
    Sci Rep, 2019 Dec 12;9(1):18955.
    PMID: 31831850 DOI: 10.1038/s41598-019-55099-6
    Heavy metal contamination in water causes severe adverse effects on human health. Millions of tons of kernel shell are produced as waste from oil palm plantation every year. In this study, palm oil kernel shell (PKS), an agricultural waste is utilized as effective adsorbent for the removal of heavy metals, namely; Cr6+, Pb2+, Cd2+ and Zn2+ from water. Different parameters of adsorptions; solution pH, adsorbent dosage, metal ions concentration and contact time were optimized. The PKS was found to be effective in the adsorption of heavy metal ions Cr6+, Pb2+, Cd2+ and Zn2+ from water with percentage removal of 98.92%, 99.01%, 84.23% and 83.45%, respectively. The adsorption capacities for Cr6+, Pb2+, Cd2+ and Zn2+ were found to be 49.65 mg/g, 43.12 mg/g, 49.62 mg/g and 41.72 mg/g respectively. Kinetics of adsorption process were determined for each metal ion using different kinetic models like the pseudo-first order, pseudo-second order and parabolic diffusion models. For each metal ion the pseudo-second order model fitted well with correlation coefficient, R2 = 0.999. Different isotherm models, namely Freundlich and Langmuir were applied for the determination of adsorption interaction between metal ions and PKS. Adsorption capacity was also determined for each of the metal ions. PKS was found to be very effective adsorbent for the treatment of heavy metal contaminated water and short time of two hours is required for maximum adsorption. This is a comprehensive study almost all the parameters of adsorptions were studied in detail. This is a cost effective and greener approach to utilize the agricultural waste without any chemical treatment, making it user friendly adsorbent.
  10. Rybalko ON, Kaladze NN, Sukhareva IA, Khoo CS
    J Neurosci Rural Pract, 2019 Oct;10(4):700-702.
    PMID: 31831992 DOI: 10.1055/s-0039-1700599
    Valproic acid or valproate is a well-recognized potent teratogen. Antenatal exposure to this drug can cause fetal valproate syndrome (FVS), which is a constellation of distinctive dysmorphic features and congenital malformations. Despite an abundance of reports and registries about this syndrome, there is lack of information from Russia, in particular, the Republic of Crimea. We herein describe two cases of FVS from our registry.
  11. Iskandar K, Sartelli M, Tabbal M, Ansaloni L, Baiocchi GL, Catena F, et al.
    World J Emerg Surg, 2019;14:50.
    PMID: 31832084 DOI: 10.1186/s13017-019-0266-x
    Antibiotics are the pillar of surgery from prophylaxis to treatment; any failure is potentially a leading cause for increased morbidity and mortality. Robust data on the burden of SSI especially those due to antimicrobial resistance (AMR) show variable rates between countries and geographical regions but accurate estimates of the incidence of surgical site infections (SSI) due to AMR and its related global economic impact are yet to be determined. Quantifying the burden of SSI treatment is an incentive to sensitize governments, healthcare systems, and the society to invest in quality improvement and sustainable development. However in the absence of a unified epidemiologically sound infection definition of SSI and a well-designed global surveillance system, the end result is a lack of accurate and reliable data that limits the comparability of estimates between countries and the possibility of tracking changes to inform healthcare professionals about the appropriateness of implemented infection prevention and control strategies. This review aims to highlight the reported gaps in surveillance methods, epidemiologic data, and evidence-based SSI prevention practices and in the methodologies undertaken for the evaluation of the economic burden of SSI associated with AMR bacteria. If efforts to tackle this problem are taken in isolation without a global alliance and data is still lacking generalizability and comparability, we may see the future as a race between the global research efforts for the advancement in surgery and the global alarming reports of the increased incidence of antimicrobial-resistant pathogens threatening to undermine any achievement.
    MeSH terms: Anti-Bacterial Agents/therapeutic use; Humans; Risk Factors; Surgical Wound Infection/drug therapy*; Surgical Wound Infection/economics*; Incidence; Health Care Costs/statistics & numerical data*; Drug Resistance, Bacterial*
  12. Sim JH, Ngan OMY, Ng HK
    J Med Educ Curric Dev, 2019 12 02;6:2382120519883887.
    PMID: 31832540 DOI: 10.1177/2382120519883887
    Introduction: A global trend in medical education is the inclusion of bioethics teaching in medical programme. The objective of this article is to describe the current state of bioethics education in the medical programme among Malaysian medical schools.

    Method: A national survey was conducted among Malaysian medical schools between January and March 2019. One representative from each medical school was invited to respond to the survey. Respondents were faculty members involved in teaching and assessment of bioethics in their medical schools, or/and in developing and coordinating bioethics curriculum. Descriptive statistics were reported.

    Findings: Out of 30 medical schools, 11 completed and returned the survey (overall response rate = 36.7%). Of these 11 schools, 6/10 (60%) were from public institutions while 5/20 (25%) were from private institutions. All except 1 school implemented a formal bioethics curriculum. A wide range of bioethics topics are currently taught in the medical programme. The majority involved in teaching bioethics were health care professionals (mainly clinicians), followed by lawyers. Lecture and attendance, respectively, are the most common teaching and assessment method. Major barriers to the implementation of bioethics education included limited qualified teaching staff (6/11 = 54.5%), no established curriculum to follow (5/11 = 45.5%), limited financial resources to hire qualified staff (4/11 = 36.4%), and no consensus among faculty members (4/11 = 36.4%).

    Conclusion: Bioethics education in Malaysia is relatively new and mostly limited by a shortage of scholars in bioethics. National support and institutional collaboration in providing bioethics training is the key to enhance the quality of bioethics education.

  13. Goh KL
    JGH Open, 2019 Dec;3(6):449.
    PMID: 31832542 DOI: 10.1002/jgh3.12282
  14. Bamber JR, Stephens TJ, Cromwell DA, Duncan E, Martin GP, Quiney NF, et al.
    BJS Open, 2019 Dec;3(6):802-811.
    PMID: 31832587 DOI: 10.1002/bjs5.50221
    BACKGROUND: Acute gallstone disease is a high-volume emergency general surgery presentation with wide variations in the quality of care provided across the UK. This controlled cohort evaluation assessed whether participation in a quality improvement collaborative approach reduced time to surgery for patients with acute gallstone disease to fewer than 8 days from presentation, in line with national guidance.

    METHODS: Patients admitted to hospital with acute biliary conditions in England and Wales between 1 April 2014 and 31 December 2017 were identified from Hospital Episode Statistics data. Time series of quarterly activity were produced for the Cholecystectomy Quality Improvement Collaborative (Chole-QuIC) and all other acute National Health Service hospitals (control group). A negative binomial regression model was used to compare the proportion of patients having surgery within 8 days in the baseline and intervention periods.

    RESULTS: Of 13 sites invited to join Chole-QuIC, 12 participated throughout the collaborative, which ran from October 2016 to January 2018. Of 7944 admissions, 1160 patients had a cholecystectomy within 8 days of admission, a significant improvement (P 

    MeSH terms: Acute Disease/therapy; Cholecystectomy/statistics & numerical data*; Emergency Service, Hospital/organization & administration*; Emergency Service, Hospital/statistics & numerical data; England; Health Plan Implementation/organization & administration; Health Plan Implementation/statistics & numerical data; Humans; Patient Admission/statistics & numerical data; State Medicine/organization & administration; State Medicine/statistics & numerical data; Time Factors; Wales; Program Evaluation; Gallstones/surgery*; Quality Improvement*; Time-to-Treatment/statistics & numerical data*; Intersectoral Collaboration
  15. Amil-Bangsa NH, Mohd-Ali B, Ishak B, Abdul-Aziz CNN, Ngah NF, Hashim H, et al.
    Optom Vis Sci, 2019 12;96(12):934-939.
    PMID: 31834153 DOI: 10.1097/OPX.0000000000001456
    SIGNIFICANCE: Total protein concentration (TPC) and tumor necrosis factor α (TNF-α) concentration in tears are correlated with severity of retinopathy. However, minimal data are available in the literature for investigating tear TPC and TNF-α concentrations in Asian individuals with different severity of nonproliferative diabetic retinopathy (NPDR).

    PURPOSE: This study evaluated differences of TPC and TNF-α concentrations in tears at different severity of NPDR among participants with diabetes in comparison with normal participants.

    METHODS: A total of 75 participants were categorized based on Early Treatment for Diabetic Retinopathy Study scale, with 15 participants representing each group, namely, normal, diabetes without retinopathy, mild NPDR, moderate NPDR, and severe NPDR. All participants were screened using McMonnies questionnaire. Refraction was conducted subjectively. Visual acuity was measured using a LogMAR chart. Twenty-five microliters of basal tears was collected using glass capillary tubes. Total protein concentration and TNF-α concentrations were determined using Bradford assay and enzyme-linked immunosorbent assay, respectively.

    RESULTS: Mean ± SD age of participants (n = 75) was 57.88 ± 4.71 years, and participants scored equally in McMonnies questionnaire (P = .90). Mean visual acuity was significantly different in severe NPDR (P = .003). Mean tear TPC was significantly lower, and mean tear TNF-α concentration was significantly higher in moderate and severe NPDR (P < .001). Mean ± SD tear TPC and TNF-α concentrations for normal were 7.10 ± 1.53 and 1.39 ± 0.24 pg/mL; for diabetes without retinopathy, 6.37 ± 1.65 and 1.53 ± 0.27 pg/mL; for mild NPDR, 6.32 ± 2.05 and 1.60 ± 0.21 pg/mL; for moderate NPDR, 3.88 ± 1.38 and 1.99 ± 0.05 pg/mL; and for severe NPDR, 3.64 ± 1.26 and 2.21 ± 0.04 pg/mL, respectively. Tear TPC and TNF-α concentrations were significantly correlated (r = -0.50, P < .0001). Visual acuity was significantly correlated with tear TPC (r = -0.236, P = .04) and TNF-α concentrations (r = 0.432, P < .0001).

    CONCLUSIONS: This cross-sectional study identified differences in tear TPC and TNF-α concentrations with increasing severity of NPDR.

    MeSH terms: Aged; Cross-Sectional Studies; Diabetic Retinopathy/classification; Diabetic Retinopathy/metabolism*; Eye Proteins/metabolism*; Female; Humans; Male; Middle Aged; Surveys and Questionnaires; Tears/metabolism*; Tumor Necrosis Factor-alpha/metabolism*; Visual Acuity
  16. Alipour E, Alimohammady F, Yumashev A, Maseleno A
    J Mol Model, 2019 Dec 13;26(1):7.
    PMID: 31834504 DOI: 10.1007/s00894-019-4267-1
    Today, drug delivery systems based on nanostructures have become the most efficient to be studied. Recent studies revealed that the fullerenes can be used as drug carriers and transport drugs in a target cell. The aim of the present work is to study the interaction of C60 fullerene containing porphyrin-like transition metal-N4 clusters (TMN4C55, TM = Fe, Co, and Ni) with a non-steroidal anti-inflammatory drug (ibuprofen (Ibp)) by employing the method of the density functional theory. Results showed that the C60 fullerene with TMN4 clusters could significantly enhance the tendency of C60 for adsorption of ibuprofen drug. Also, our ultraviolet-visible results show that the electronic spectra of Ibp/TMN4C55 complexes exhibit a blue shift toward lower wavelengths (higher energies). It was found that the NiN4C55 fullerene had high chemical reactivity, which was important for binding of the drug onto the carrier surface. In order to gain insight into the binding features of Ibp/TMN4C55 complexes, the atoms in molecules analysis was also performed. Our results exhibit the electrostatic features of the Ibp/TMN4C55 bonding. Consequently, this study demonstrated that the TMN4C55 fullerenes could be used as potential carriers for delivery of Ibp drug in the nanomedicine domain. Graphical Abstract The TMN4C55 (TM=Fe, Co, and Ni) fullerenes could be used as potential carriers for delivery of ibuprofen drug in the nanomedicine domain.
    MeSH terms: Adsorption/drug effects; Humans; Ibuprofen/therapeutic use; Ibuprofen/chemistry*; Inflammation/drug therapy*; Metals/therapeutic use; Metals/chemistry; Models, Molecular; Porphyrins/therapeutic use; Porphyrins/chemistry*; Drug Delivery Systems*; Fullerenes/therapeutic use; Fullerenes/chemistry*; Nanostructures/therapeutic use; Nanostructures/chemistry; Static Electricity; Coordination Complexes/therapeutic use; Coordination Complexes/chemistry
  17. Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu, Cross-Disorder Group of the Psychiatric Genomics Consortium
    Cell, 2019 Dec 12;179(7):1469-1482.e11.
    PMID: 31835028 DOI: 10.1016/j.cell.2019.11.020
    Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
    MeSH terms: Mental Disorders/genetics*; Humans; Genetic Predisposition to Disease*; Quantitative Trait Loci*; Genome-Wide Association Study; Neurogenesis; Genetic Pleiotropy*
  18. Gao Y, Zhang W, Liu C, Li G
    Sci Rep, 2019 12 11;9(1):18844.
    PMID: 31827114 DOI: 10.1038/s41598-019-54289-6
    Resistance to tamoxifen is a major clinical challenge. Research in recent years has identified epigenetic changes as mediated by dysregulated miRNAs that can possibly play a role in resistance to tamoxifen in breast cancer patients expressing estrogen receptor (ER). We report here elevated levels of EMT markers (vimentin and ZEB1/2) and reduced levels of EMT-regulating miR-200 (miR-200b and miR-200c) in ER-positive breast cancer cells, MCF-7, that were resistant to tamoxifen, in contrast with the naïve parental MCF-7 cells that were sensitive to tamoxifen. Further, we established regulation of c-MYB by miR-200 in our experimental model. C-MYB was up-regulated in tamoxifen resistant cells and its silencing significantly decreased resistance to tamoxifen and the EMT markers. Forced over-expression of miR-200b/c reduced c-MYB whereas reduced expression of miR-200b/c resulted in increased c-MYB We further confirmed the results in other ER-positive breast cancer cells T47D cells where forced over-expression of c-MYB resulted in induction of EMT and significantly increased resistance to tamoxifen. Thus, we identify a novel mechanism of tamoxifen resistance in breast tumor microenvironment that involves miR-200-MYB signaling.
    MeSH terms: Breast Neoplasms/drug therapy; Breast Neoplasms/genetics; Breast Neoplasms/metabolism*; Breast Neoplasms/physiopathology; Female; Humans; Receptors, Estrogen; Tamoxifen/therapeutic use*; Signal Transduction; Gene Expression Regulation, Neoplastic; Antineoplastic Agents, Hormonal/therapeutic use; Drug Resistance, Neoplasm*; Proto-Oncogene Proteins c-myb/genetics; MicroRNAs/metabolism*; Cell Line, Tumor; Cell Proliferation; Epithelial-Mesenchymal Transition*; Tumor Microenvironment; MCF-7 Cells
  19. Ng SY, Lee AYW
    Front Cell Neurosci, 2019;13:528.
    PMID: 31827423 DOI: 10.3389/fncel.2019.00528
    Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve the bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.
  20. Sharif AA, Unyah NZ, Nordin N, Basir R, Wana MN, Alapid Ahmad A, et al.
    PMID: 31827548 DOI: 10.1155/2019/2916547
    Background: Toxoplasmosis remains widely distributed globally and is one of the major neglected parasitic zoonotic infections. The infection is still endemic in most parts of the world due to poor control as well as challenges of the currently used medications which can be overcome by using natural products. This study evaluated the effect of ethanolic extract from the stem of Tinospora crispa (EETC) on host cell invasion and intracellular replication of Toxoplasma gondii.

    Method: The stem powder of T. crispa was soaked in absolute ethanol for 72 hours. The resulting ethanolic extract was screened for the presence of phytochemicals. Vero cells monolayer in 96-well plate was infected with RH strain of T. gondii and treated with concentrations of the EETC, Veratrine alkaloid, and clindamycin ranging from 1.56 to 200 μg/mL. MTT assay was conducted after 24 hours to evaluate the cytotoxicity and antiparasitic activities of the EETC. Four and 24 hours treatment models were adapted to assess the infection index and intracellular proliferation of T.

    Results: The study revealed that the EETC had no cytotoxic effects on Vero cells with IC50 = 179 μg/mL, as compared to clindamycin (IC50 = 116.5 μg/mL) and Veratrine alkaloid (IC50 = 60.4 μg/mL). The EETC had good anti-toxoplasma activities with IC50 = 6.31 μg/mL in comparison with clindamycin (IC50 = 8.33 μg/mL) and Veratrine alkaloid (IC50 = 14.25 μg/mL). The EETC caused more than 70% and 80% reduction in infection index and intracellular proliferation in both treatment models, respectively.

    Conclusion: This in vitro study showed that the EETC contains promising phytochemicals effective against T. gondii and safe to the host cells.

    MeSH terms: Ethanol; Animals; Anti-Infective Agents; Antiparasitic Agents; Biological Products; Clindamycin; Plant Extracts; Toxoplasma; Toxoplasmosis; Veratrine; Vero Cells; Zoonoses; Inhibitory Concentration 50; Tinospora; Cell Proliferation; Phytochemicals
External Links