Browse publications by year: 2017

  1. Abdul Majid MA, Mahboob T, Mong BG, Jaturas N, Richard RL, Tian-Chye T, et al.
    PLoS One, 2017;12(2):e0169448.
    PMID: 28212409 DOI: 10.1371/journal.pone.0169448
    Data on the distribution of free-living amoebae is still lacking especially in Southeast Asian region. The aquatic environment revealed a high occurrence of free-living amoebae (FLA) due to its suitable condition and availability of food source, which subsequently causes infection to humans. A total of 94 water samples consisted of both treated and untreated from Laos (31), Myanmar (42), and Singapore (21) were investigated for the presence of pathogenic FLA. Each water sample was filtered and cultured onto non-nutrient agar seeded with live suspension of Escherichia coli and incubated at room temperature. Morphological identification was conducted for both trophozoites and cysts via microscopic stains (Giemsa and immunofluorescence). The presence of Naegleria-like structures was the most frequently encountered in both treated and untreated water samples, followed by Acanthamoeba-like and Vermamoeba-like features. To identify the pathogenic isolates, species-specific primer sets were applied for molecular identification of Acanthamoeba, Naegleria, and Vermamoeba. The pathogenic species of Acanthamoeba lenticulata and A. triangularis were detected from untreated water samples, while Vermamoeba vermiformis was found in both treated and untreated water samples. Our results suggested that poor water quality as well as inadequate maintenance and treatment might be the cause of this alarming problem since chlorine disinfection is ineffective in eradicating these amoebas in treated water samples. Regular monitoring and examination of water qualities are necessary in order to control the growth, hence, further preventing the widespread of FLA infections among the public.
    MeSH terms: Amoeba/classification; Amoeba/genetics; Amoeba/isolation & purification*; Base Sequence; Humans; Phylogeny; Water Microbiology; Asian Continental Ancestry Group
  2. Amin OS, Shwani SS
    BMJ Case Rep, 2017 Feb 15;2017.
    PMID: 28202488 DOI: 10.1136/bcr-2017-219433
    MeSH terms: Adolescent; Humans; Male; Myoclonus/complications*; Ocular Motility Disorders/complications*; Ocular Motility Disorders/diagnosis; Gait Ataxia/complications*
  3. Karimian H, Arya A, Fadaeinasab M, Razavi M, Hajrezaei M, Karim Khan A, et al.
    Drug Des Devel Ther, 2017;11:337-350.
    PMID: 28203057 DOI: 10.2147/DDDT.S121518
    BACKGROUND: The aim of this study was to evaluate the anticancer potential of Kelussia odoratissima. Several in vitro and in vivo biological assays were applied to explore the direct effect of an extract and bioactive compound of this plant against breast cancer cells and its possible mechanism of action.

    MATERIALS AND METHODS: K. odoratissima methanol extract (KME) was prepared, and MTT assay was used to evaluate the cytotoxicity. To identify the cytotoxic compound, a bioassay-guided investigation was performed on methanol extract. 8-Hydroxy-ar-turmerone was isolated as a bioactive compound. In vivo study was performed in the breast cancer rat model. LA7 cell line was used to induce the breast tumor. Histopathological and expression changes of PCNA, Bcl-2, Bax, p27 and p21 and caspase-3 were examined. The induction of apoptosis was tested using Annexin V-fluorescein isothiocyanate (FITC) assay. To confirm the intrinsic pathway of apoptosis, caspase-7 and caspase-9 assays were utilized. In addition, cell cycle arrest was evaluated.

    RESULTS: Our results demonstrated that K. odoratissima has an obvious effect on the arrest of proliferation of cancer cells. It induced apoptosis, transduced the cell death signals, decreased the threshold of mitochondrial membrane potential (MMP), upregulated Bax and downregulated Bcl-2.

    CONCLUSION: This study demonstrated that K. odoratissima exhibits antitumor activity against breast cancer cells via cell death and cell cycle arrest.

    MeSH terms: Animals; Antineoplastic Agents, Phytogenic/isolation & purification; Antineoplastic Agents, Phytogenic/pharmacology*; Antineoplastic Agents, Phytogenic/chemistry; Cell Survival/drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Mammary Neoplasms, Experimental/drug therapy; Mammary Neoplasms, Experimental/metabolism; Mammary Neoplasms, Experimental/pathology*; Molecular Conformation; Plant Extracts/isolation & purification; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Structure-Activity Relationship; Rats, Sprague-Dawley; Apoptosis/drug effects*; Apiaceae/chemistry*; Cell Line, Tumor; Cell Proliferation/drug effects; Cyclin-Dependent Kinase Inhibitor p21/metabolism*; Cyclin-Dependent Kinase Inhibitor p27/metabolism*; Rats; S Phase Cell Cycle Checkpoints/drug effects*
  4. Norhisham NF, Chong CY, Safuan S
    BMC Clin Pathol, 2017;17:2.
    PMID: 28203117 DOI: 10.1186/s12907-017-0041-4
    BACKGROUND: Detection of vascular invasion by hematoxylin and eosin staining is the current pathological assessment practice to diagnose breast carcinoma. However, conventional hematoxylin and eosin staining failed to distinguish between blood vessel invasion and lymphatic vessel invasion. Both are important prognostic criteria however with different outcomes. The aim of this study is to distinguish between blood vessel invasion and lymphatic vessel invasion using conventional assessment and immunohistochemical markers. The prognostic significance of both circulatory invasions in invasive breast carcinoma was also investigated.

    METHODS: Consecutive sections of breast carcinoma samples from 58 patients were stained with CD34 and D240 to stain blood and lymphatic vessels respectively. Hematoxylin and eosin staining was carried out on another consecutive section as conventional staining.

    RESULTS: Although blood vessel density is higher in the sections (median = 10.3 vessels) compared to lymphatic vessel density (median = 0.13), vessel invasion is predominantly lymphatic invasion (69.8 and 55.2% respectively). Interestingly, peritumoral lymphatic vessel density and peritumoral lymphatic invasion was significantly associated with distant metastasis (p = 0.049 and p = 0.05 respectively). The rate of false positive and false negative interpretation by hematoxylin and eosin was 46.7 and 53.3% respectively.

    CONCLUSIONS: Lymphatic vessel invasion is a strong prognostic markers of breast carcinoma invasion and the use of immunohistochemical markers increase the rate and accuracy of detection.

  5. Abdullah S, Wong WF, Tan CT
    Mult Scler Int, 2017;2017:1359761.
    PMID: 28203460 DOI: 10.1155/2017/1359761
    Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients' clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT) cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p < 0.001). Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p < 0.001). Longitudinally extensive spinal cord lesions (LESCLs) on MRI were also more common in the seropositive group, 29/40 (72.50%; p = 0.004). Only 2/40 (5.00%) had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p = 0.003). The relapse rate and Expanded Disability Status Scale (EDSS) were also higher in the seropositive group (5.43 versus 3.17, p = 0.005; 4.07 versus 2.51, p = 0.006, resp.). Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS.
  6. Munisamy M, Krishnan K, Selvaratnam G, Panza A, Pongpanich S, Jimba M
    Occup Med (Lond), 2017 Feb 15.
    PMID: 28204665 DOI: 10.1093/occmed/kqx015
  7. Abbood AA, Kassim AB, Jawad HSA, Manap YA, Sazili AQ
    Poult Sci, 2017 Jun 01;96(6):1767-1782.
    PMID: 28204764 DOI: 10.3382/ps/pew460
    An experiment was carried out to estimate the meat quality characteristics of village chickens (Gallus gallus) fed diets supplemented with dry leaves of Borreria latifolia (BL) used as a potential antioxidant source in chicken feed. In this study, 252 sexed 9-week-old village chickens with mean live body weight of 1,525.4 g for males and 1,254.1 g for females were divided into 7 groups (each group 18 birds) for each sex represented in 2 experiments. The first experiment was to evaluate the antioxidant activity of BL and the effect on meat quality through a comparison with Rosmarinus officinalis (RO); hence, 3 groups were conducted and included: T1 (control), basal diet without supplementation; T2, basal diet with 1% of BL; T3, basal diet with 1% of RO. T2 and T3 significantly affect pH value, lipid oxidation, cooking loss, and overall acceptability compared to T1, while no significant difference was observed between the dietary groups in respect of drip loss, color, tenderness, fatty acid profile, and meat composition. Furthermore, a significant effect of sex on lipid oxidation, pH, yellowness, and fatty acid profile was observed. There was no significant effect of sex on WHC, tenderness, lightness, redness, and sensory evaluation. A significant influence of postmortem aging period was detected on lipid oxidation, pH, tenderness, cooking loss, and redness. The obtained result in this study revealed a significance in the interaction of herb by sex in pH parameter and between herb and sex, herb by aging period, sex by aging period, and the herb by sex by aging period interactions with regard to lipid oxidation test. The second experiment was to estimate the effect of 3 different levels of BL on meat quality. Four groups were provided and involved: T1 (control), basal diet without supplementation; T2, basal diet with 1.5% of BL; T3, basal diet with 2% of BL; and T4, basal diet with 2.5% of BL. The result of this study showed a significant effect (P
    MeSH terms: Animals; Animal Feed/analysis; Animal Nutritional Physiological Phenomena; Antioxidants/administration & dosage; Antioxidants/pharmacology; Chickens*; Diet/veterinary; Female; Malaysia; Male; Meat/analysis*; Sex Factors; Dietary Supplements; Rubiaceae*; Rosmarinus
  8. Nordin N, Yusof NA, Abdullah J, Radu S, Hushiarian R
    AMB Express, 2017 Dec;7(1):41.
    PMID: 28205102 DOI: 10.1186/s13568-017-0339-8
    An earlier electrochemical mechanism of DNA detection was adapted and specified for the detection of Vibrio parahaemolyticus in real samples. The reader, based on a screen printed carbon electrode, was modified with polylactide-stabilized gold nanoparticles and methylene blue was employed as the redox indicator. Detection was assessed using a microprocessor to measure current response under controlled potential. The fabricated sensor was able to specifically distinguish complementary, non-complementary and mismatched oligonucleotides. DNA was measured in the range of 2.0 × 10(-8)-2.0 × 10(-13) M with a detection limit of 2.16 pM. The relative standard deviation for 6 replications of differential pulse voltammetry (DPV) measurement of 0.2 µM complementary DNA was 4.33%. Additionally, cross-reactivity studies against various other food-borne pathogens showed a reliably sensitive detection of the target pathogen. Successful identification of Vibrio parahaemolyticus (spiked and unspiked) in fresh cockles, combined with its simplicity and portability demonstrate the potential of the device as a practical screening tool.
    MeSH terms: Animals; Carbon; DNA; Electrodes; Gold; Methylene Blue; Microcomputers; Oligonucleotides; Oxidation-Reduction; Polyesters; Vibrio parahaemolyticus; DNA, Complementary; Cardiidae; Metal Nanoparticles; Limit of Detection
  9. Shafie AA, Yeo HY, Coudeville L, Steinberg L, Gill BS, Jahis R, et al.
    Pharmacoeconomics, 2017 May;35(5):575-589.
    PMID: 28205150 DOI: 10.1007/s40273-017-0487-3
    BACKGROUND: Dengue disease poses a great economic burden in Malaysia.

    METHODS: This study evaluated the cost effectiveness and impact of dengue vaccination in Malaysia from both provider and societal perspectives using a dynamic transmission mathematical model. The model incorporated sensitivity analyses, Malaysia-specific data, evidence from recent phase III studies and pooled efficacy and long-term safety data to refine the estimates from previous published studies. Unit costs were valued in $US, year 2013 values.

    RESULTS: Six vaccination programmes employing a three-dose schedule were identified as the most likely programmes to be implemented. In all programmes, vaccination produced positive benefits expressed as reductions in dengue cases, dengue-related deaths, life-years lost, disability-adjusted life-years and dengue treatment costs. Instead of incremental cost-effectiveness ratios (ICERs), we evaluated the cost effectiveness of the programmes by calculating the threshold prices for a highly cost-effective strategy [ICER <1 × gross domestic product (GDP) per capita] and a cost-effective strategy (ICER between 1 and 3 × GDP per capita). We found that vaccination may be cost effective up to a price of $US32.39 for programme 6 (highly cost effective up to $US14.15) and up to a price of $US100.59 for programme 1 (highly cost effective up to $US47.96) from the provider perspective. The cost-effectiveness analysis is sensitive to under-reporting, vaccine protection duration and model time horizon.

    CONCLUSION: Routine vaccination for a population aged 13 years with a catch-up cohort aged 14-30 years in targeted hotspot areas appears to be the best-value strategy among those investigated. Dengue vaccination is a potentially good investment if the purchaser can negotiate a price at or below the cost-effective threshold price.

    MeSH terms: Adolescent; Adult; Cost-Benefit Analysis; Dengue/economics; Dengue/prevention & control*; Humans; Malaysia; Models, Theoretical*; Vaccination/economics; Vaccination/methods; Health Care Costs; Cost of Illness*; Immunization Programs/economics; Dengue Vaccines/administration & dosage*; Dengue Vaccines/economics; Young Adult
  10. Vale FF, Nunes A, Oleastro M, Gomes JP, Sampaio DA, Rocha R, et al.
    Sci Rep, 2017 02 16;7:42471.
    PMID: 28205536 DOI: 10.1038/srep42471
    Helicobacter pylori genetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements of H. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found in H. pylori isolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6-33.0 Kbp, consisting of 27-39 open reading frames. A 36.6% GC was found in prophages in contrast to 39% in H. pylori genome. Remarkably a conserved integration site was found in over 50% of the cases. Nearly 40% of the prophages harbored insertion sequences (IS) previously described in H. pylori. Tandem repeats were frequently found in the intergenic region between the prophage at the 3' end and the bacterial gene. Furthermore, prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. Evidence of recombination was detected within the genome of some prophages, resulting in genome mosaics composed by different populations, which may yield additional H. pylori phenotypes.
    MeSH terms: Mosaicism; Phylogeny; Mutagenesis, Insertional*; Open Reading Frames; Helicobacter pylori/virology*; Genome, Viral*; Sequence Analysis, DNA; Prophages/genetics*
  11. van der Ent A, Callahan DL, Noller BN, Mesjasz-Przybylowicz J, Przybylowicz WJ, Barnabas A, et al.
    Sci Rep, 2017 Feb 16;7:41861.
    PMID: 28205587 DOI: 10.1038/srep41861
    The extraordinary level of accumulation of nickel (Ni) in hyperaccumulator plants is a consequence of specific metal sequestering and transport mechanisms, and knowledge of these processes is critical for advancing an understanding of transition element metabolic regulation in these plants. The Ni biopathways were elucidated in three plant species, Phyllanthus balgooyi, Phyllanthus securinegioides (Phyllanthaceae) and Rinorea bengalensis (Violaceae), that occur in Sabah (Malaysia) on the Island of Borneo. This study showed that Ni is mainly concentrated in the phloem in roots and stems (up to 16.9% Ni in phloem sap in Phyllanthus balgooyi) in all three species. However, the species differ in their leaves - in P. balgooyi the highest Ni concentration is in the phloem, but in P. securinegioides and R. bengalensis in the epidermis and in the spongy mesophyll (R. bengalensis). The chemical speciation of Ni2+ does not substantially differ between the species nor between the plant tissues and transport fluids, and is unambiguously associated with citrate. This study combines ion microbeam (PIXE and RBS) and metabolomics techniques (GC-MS, LC-MS) with synchrotron methods (XAS) to overcome the drawbacks of the individual techniques to quantitatively determine Ni distribution and Ni2+ chemical speciation in hyperaccumulator plants.
    MeSH terms: Malaysia; Nickel/analysis; Nickel/metabolism*; Plant Roots/metabolism; Plant Roots/chemistry; Angiosperms/metabolism*; Angiosperms/chemistry; Phloem/metabolism; Phloem/chemistry
  12. Carpentier P, van Bellen B, Karetova D, Hanafiah H, Enriquez-Vega E, Kirienko A, et al.
    Int Angiol, 2017 Oct;36(5):402-409.
    PMID: 28206732 DOI: 10.23736/S0392-9590.17.03801-9
    BACKGROUND: Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF.

    METHODS: In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire.

    RESULTS: A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P<0.0001) was found for lower limb discomfort (-3.33 cm for MPFF 1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg).

    CONCLUSIONS: MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.

    MeSH terms: Administration, Oral; Adult; Aged; Chronic Disease; Double-Blind Method; Female; Flavonoids/administration & dosage*; Flavonoids/adverse effects; Humans; International Cooperation; Male; Middle Aged; Pain Measurement; Quality of Life; Surveys and Questionnaires; Vascular Diseases/drug therapy*; Vascular Diseases/physiopathology; Treatment Outcome; Lower Extremity/blood supply*; Lower Extremity/physiopathology; Young Adult; Pain Management
  13. Ch'ng CC, Wong SM, Lee YY
    Cutis, 2017 Jan;99(1):E1-E3.
    PMID: 28207013
    MeSH terms: Genital Diseases, Male/diagnosis*; Genital Diseases, Male/pathology; Humans; Male; Middle Aged; Mouth Diseases/diagnosis*; Mouth Diseases/pathology; Pain/etiology; Pemphigus/diagnosis*; Pemphigus/pathology
  14. Chan CY, Kwan MK, Saw LB, Paisal H
    Clin Spine Surg, 2017 03;30(2):E138-E147.
    PMID: 28207623 DOI: 10.1097/BSD.0b013e3182aa6860
    BACKGROUND CONTEXT: The clinical application of recombinant bone morphogenetic protein in spinal surgery has been shown to be safe and effective. However, its use in minimally invasive spine surgery has been limited to anterior interbody fusion procedures. To date, no study has evaluated the feasibility of percutaneous posterolateral fusion in the spine utilizing recombinant bone morphogenetic protein-2 (rhBMP-2).

    PURPOSE: To evaluate the feasibility of percutaneous posterolateral fusion in the spine utilizing rhBMP-2.

    STUDY DESIGN: Animal study.

    METHODS: This is an animal research model involving 32 New Zealand white rabbits stratified into 4 study groups: control, autogenous iliac crest bone graft (ICBG), demineralized bone matrix (DBM), and rhBMP-2 groups, with 8 study subjects per group. The rhBMP-2 group was subdivided into the open technique (right side) and the percutaneous technique groups (left side). Fusion was graded at 6 weeks and 3 months after plain radiography, computed tomography, and clinical assessment with the following grading system: grade A, no bone formation; grade B, non-bridging bone formation; grade C, fusion; and grade D, fusion with ectopic bone formation.

    RESULTS: No fusion was noted in the placebo and the DBM groups. However, in the DBM group, bone formation occurred in 37.5% of the subjects. The rhBMP-2 group had a higher fusion rate compared with the ICBG group at 6 weeks and 3 months. The fusion rate for the ICBG, the rhBMP-2 (open), and the rhBMP-2 (percutaneous) groups were 37.5%, 87.5%, and 50.0% at 6 weeks and 50.0%, 100.0%, and 62.5% at 3 months, respectively. Ectopic bone formation occurred in 12.5% of the cases in the rhBMP-2 (percutaneous) group and in 25.0% of the cases in the rhBMP-2 (open) group.

    CONCLUSIONS: Usage of rhBMP-2 is feasible for percutaneous posterolateral fusion of the lumbar spine in this animal model. However, a more precise delivery system might improve the fusion rate when the percutaneous technique is used. A significant rate of ectopic bone formation occurred when rhBMP-2 was used.

    MeSH terms: Animals; Disease Models, Animal; Feasibility Studies; Follow-Up Studies; Rabbits; Radiography; Recombinant Proteins/therapeutic use; Spinal Diseases/therapy; Spinal Fusion/methods*; Time Factors; Tomography Scanners, X-Ray Computed; Bone Transplantation; Transforming Growth Factor beta/therapeutic use*; Bone Morphogenetic Protein 2/therapeutic use*
  15. Chan CYW, Aziz I, Chai FW, Kwan MK
    Spine (Phila Pa 1976), 2017 Feb 15;42(4):E248-E252.
    PMID: 28207671 DOI: 10.1097/BRS.0000000000001748
    STUDY DESIGN: Case report.

    OBJECTIVE: To report the successful rehabilitation and the training progress of an elite high performance martial art exponent after selective thoracic fusion for Adolescent Idiopathic Scoliosis (AIS).

    SUMMARY OF BACKGROUND DATA: Posterior spinal fusion for AIS will result in loss of spinal flexibility. The process of rehabilitation after posterior spinal fusion for AIS remains controversial and there are few reports of return to elite sports performance after posterior spinal fusion for AIS.

    METHODS: We report a case of a 25-year-old lady who was a national Wu Shu exponent. She was a Taolu (Exhibition) exponent. She underwent Selective Thoracic Fusion (T4 to T12) using alternate level pedicle screw placement augmented with autogenous local bone graft in June 2014. She commenced her training at 3-month postsurgery and the intensity of her training was increased after 6 months postsurgery. We followed her up to 2 years postsurgery and showed no instrumentation failure or lost of correction.

    RESULTS: After selective thoracic fusion, her training process consisted of mainly speed training, core strengthening, limb strengthening, and flexibility exercises. At 17 months of postoperation, she participated in 13th World Wu Shu Championship 2015 and won the silver medal.

    CONCLUSION: Return to elite high-performance martial arts sports was possible after selective thoracic fusion for AIS. The accelerated and intensive training regime did not lead to any instrumentation failure and complications.

    LEVEL OF EVIDENCE: 2.

    MeSH terms: Adult; Athletic Injuries/surgery*; Female; Humans; Lumbar Vertebrae/physiopathology; Lumbar Vertebrae/surgery; Retrospective Studies; Scoliosis/diagnosis; Scoliosis/surgery*; Thoracic Vertebrae/physiopathology*; Thoracic Vertebrae/surgery*; Treatment Outcome; Athletes*; Pedicle Screws/adverse effects
  16. Butcher AL, Koh CT, Oyen ML
    J Mech Behav Biomed Mater, 2017 May;69:412-419.
    PMID: 28208112 DOI: 10.1016/j.jmbbm.2017.02.007
    Electrospinning is a simple and efficient process for producing sub-micron fibres. However, the process has many variables, and their effects on the non-woven mesh of fibres is complex. In particular, the effects on the mechanical properties of the fibre meshes are poorly understood. This paper conducts a parametric study, where the concentration and bloom strength of the gelatin solutions are varied, while all electrospinning process parameters are held constant. The effects on the fibrous meshes are monitored using scanning electron microscopy and mechanical testing under uniaxial tension. Mesh mechanical properties are relatively consistent, despite changes to the solutions, demonstrating the robustness of electrospinning. The gel strength of the solution is shown to have a statistically significant effect on the morphology, stiffness and strength of the meshes, while the fibre diameter has surprisingly little influence on the stiffness of the meshes. This experimental finding is supported by finite element analysis, demonstrating that the stiffness of the meshes is controlled by the volume fraction, rather than fibre diameter. Our results demonstrate the importance of understanding how electrospinning parameters influence the pore size of the meshes, as controlling fibre diameter alone is insufficient for consistent mechanical properties.
    MeSH terms: Gelatin/analysis*; Materials Testing*; Microscopy, Electron, Scanning; Finite Element Analysis; Tissue Engineering
  17. Fahmy O, Schubert T, Khairul-Asri MG, Stenzl A, Gakis G
    Int J Urol, 2017 04;24(4):320-323.
    PMID: 28208217 DOI: 10.1111/iju.13307
    The surgical treatment of a long proximal ureteral stricture is a challenging situation for reconstructive surgeons. Despite the underlying morbidities, ileal interposition and autotransplantation are the options available to treat complex cases of long segment ureteral stricture. Buccal mucosa has shown excellent results in urethroplasty. However, its use in ureteral reconstruction is infrequent. We report on a 64-year-old female patient with multiple comorbidities and prior abdominal surgeries for Crohn's disease who underwent a successful total substitution of a long segment of the proximal ureter using buccal mucosa. Regular postoperative isotope scans showed improvement in renal function. Based on the pleasant outcome of this case and review of the literature, buccal mucosa might be a viable option with low morbidity in selected cases.
    MeSH terms: Constriction, Pathologic/diagnosis; Constriction, Pathologic/surgery; Female; Humans; Middle Aged; Mouth Mucosa/transplantation*; Urologic Surgical Procedures/methods*; Ureter/pathology; Ureter/transplantation*; Ureteral Obstruction/surgery*; Urography; Treatment Outcome; Reconstructive Surgical Procedures/methods*
  18. Ghasemzadeh-Moghaddam H, van Wamel W, van Belkum A, Hamat RA, Neela VK
    Eur J Clin Microbiol Infect Dis, 2017 Mar;36(3):451-458.
    PMID: 27815779 DOI: 10.1007/s10096-016-2817-3
    The humoral immune response against 43 staphylococcal antigens was compared among hospitalized patients where none of them had any staphylococcal infection on the day of admission with or without nasal Staphylococcus aureus carriage. Fifty-nine carriers and 59 matched non-carriers were studied. The carriers harbored S. aureus of 35 different spa types, including three t037/ST239 methicillin-resistant S. aureus (MRSA) (5.1%). Among the 118 patients, 31 acquired S. aureus during hospitalization. In colonized and non-colonized patients, unique patterns of S. aureus-specific immune responses were observed. The mean fluorescence indices (MFIs) of antibodies against 36/43 (83.7%) antigens were seen to be elevated among carriers. The MFI among carriers with acquisition was significantly higher for staphylococcal superantigen-like protein 5 (SSL5, p = 0.028) when compared to carriers without acquisition. High antibody levels against staphylococcal enterotoxin A (SEA) among carriers illustrate its role as a superantigen in both infection and colonization. We also report a dynamic immune response in S. aureus-carrying patients against the recently reported formyl peptide receptor-like inhibitory (FLIPr)-like protein. In the current study, the dynamics of antibodies against staphylococcal antigens among carrier patients seem quite similar to non-carrier patients. To better understand the dynamic immunogenicity during S. aureus infection and colonization, artificial colonization studies and investigation of the changes in the levels of antibodies against other staphylococcal antigens are recommended.
    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Bacterial/blood*; Antigens, Bacterial/immunology; Carrier State/immunology*; Carrier State/microbiology; Female; Humans; Male; Middle Aged; Nasal Mucosa/microbiology; Staphylococcal Infections/immunology*; Staphylococcal Infections/microbiology; Staphylococcus aureus/immunology*; Staphylococcus aureus/isolation & purification*; Young Adult; Immunity, Humoral*
  19. Qian M, Zhang H, Kham SK, Liu S, Jiang C, Zhao X, et al.
    Genome Res, 2017 02;27(2):185-195.
    PMID: 27903646 DOI: 10.1101/gr.209163.116
    Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole-transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54.1% of patients (n = 125), 31 of which have not been reported previously. In particular, we described a distinct ALL subtype with a characteristic gene expression signature predominantly driven by chromosomal rearrangements of the ZNF384 gene with histone acetyltransferases EP300 and CREBBP ZNF384-rearranged ALL showed significant up-regulation of CLCF1 and BTLA expression, and ZNF384 fusion proteins consistently showed higher activity to promote transcription of these target genes relative to wild-type ZNF384 in vitro. Ectopic expression of EP300-ZNF384 and CREBBP-ZNF384 fusion altered differentiation of mouse hematopoietic stem and progenitor cells and also potentiated oncogenic transformation in vitro. EP300- and CREBBP-ZNF384 fusions resulted in loss of histone lysine acetyltransferase activity in a dominant-negative fashion, with concomitant global reduction of histone acetylation and increased sensitivity of leukemia cells to histone deacetylase inhibitors. In conclusion, our results indicate that gene fusion is a common class of genomic abnormalities in childhood ALL and that recurrent translocations involving EP300 and CREBBP may cause epigenetic deregulation with potential for therapeutic targeting.
    MeSH terms: Animals; Female; Humans; Male; Promoter Regions, Genetic; Translocation, Genetic/genetics; Oncogene Proteins, Fusion/genetics; Trans-Activators/genetics*; Gene Expression Regulation, Leukemic; Genomics; E1A-Associated p300 Protein/genetics*; CREB-Binding Protein/genetics*; Mice; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology; Transcriptome/genetics
  20. Mohamad Fairus AK, Choudhary B, Hosahalli S, Kavitha N, Shatrah O
    Biochimie, 2017 Apr;135:154-163.
    PMID: 28196676 DOI: 10.1016/j.biochi.2017.02.003
    Dihydroorotate dehydrogenase (DHODH) is the key enzyme in de novo biosynthesis of pyrimidine in both prokaryotes and eukaryotes. The de novo pathway of pyrimidine biosynthesis is essential in cancer cells proliferation. Leflunomide is an approved DHODH inhibitor that has been widely used for the treatment of arthritis. Similarly, brequinar sodium is another DHODH inhibitor that showed anti-tumour effect in MC38 colon carcinoma cells when used in combination with fluorouracil. Despite the potential role of DHODH inhibitors in cancer therapy, their mechanisms of action remain obscure and await further elucidation. Here, we evaluated the effect of DHODH inhibitors on the production of ATP and ROS in sensitive and non-sensitive breast cancer cells. Subsequently, the effects of DHODH inhibitors on cell cycle as well as on signalling molecules such as p53, p65 and STAT6 were evaluated in sensitive T-47D and non-sensitive MDAMB-436 cells. The correlations between DHODH protein expression, proliferation speed and sensitivity to DHODH inhibitors were also investigated in a panel of cancer cell lines. DHODH inhibitors-sensitive T-47D and MDAMB-231 cells appeared to preserve ROS production closely to endogenous ROS level whereas the opposite was observed in non-sensitive MDAMB-436 and W3.006 cells. In addition, we observed approximately 90% of intracellular ATP depletion in highly sensitive T-47D and MDAMB-231 cells compared to non-sensitive MDAMB-436 cells. There was significant over-expression of p53, p65 and STAT6 signalling molecules in sensitive cells which may be involved in mediating the S-phase arrest in cell cycle progression. The current study suggests that DHODH inhibitors are most effective in cells that express high levels of DHODH enzyme. The inhibition of cell proliferation by these inhibitors appears to be accompanied by ROS production as well as ATP depletion. The increase in expression of signalling molecules observed may be due to pyrimidine depletion which subsequently leads to cell cycle arrest at S-phase.
    MeSH terms: Biphenyl Compounds; Cell Cycle; Cell Line; Fluorouracil; Pyrimidines; Tumor Suppressor Protein p53; Reactive Oxygen Species; Oxidoreductases Acting on CH-CH Group Donors; Cell Proliferation; Eukaryota; Cell Cycle Checkpoints
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