Browse publications by year: 2019

  1. Md Pauzi SH, Saari HN, Roslan MR, Syed Khair Azman Jamalulil SNS, Tauan IS, Mohd Rusli FA, et al.
    Malays J Pathol, 2019 Aug;41(2):133-138.
    PMID: 31427548
    INTRODUCTION: Evaluation of HER2 status in breast cancer using immunohistochemistry (IHC) and in-situ-hybridisation (ISH) study is important to establish prognosis and to select patient for targeted therapy.

    OBJECTIVE: The study aims to determine the concordance between HER2 protein IHC score and its gene status by dual-colour dual-hapten in-situ-hybridization (DDISH) study.

    MATERIALS AND METHODS: Retrospective study was performed on 767 referred breast cancer cases over a period of five years. The HER2 IHC score (the initial and repeat test score) and the results of HER2 gene status by DDISH were retrieved from the histopathological reports. The agreement between initial IHC score with repeat test score was measured using Cohen Kappa. Chi square test analyzed the association between HER2 IHC score with its gene status by DDISH.

    RESULTS: The concordance of HER2 IHC score between the initial and repeat test were 52.7% and 89.4% for IHC score 2+ and 3+ respectively. There was moderate agreement of HER2 IHC score between the initial and repeat test score (ϰ = 0.526, p<0.001). A significant association noted between HER2 IHC score with its gene status by DDISH (p<0.001). Only 56 out of 207 cases (27.1%) with 2+ IHC score showed HER2 gene amplification while the majority of cases with 3+ IHC score were gene-amplified (446 out of 451, 98.9%).

    CONCLUSION: ISH study should be done in all IHC-equivocal cases (2+) to select patient for targeted therapy. Gene amplification must also be confirmed in IHC-positive cases (3+) to prevent from giving non-effective treatment with possible adverse effects to patient with non-amplified HER2 gene.

    MeSH terms: Breast Neoplasms; Color; Gene Amplification; Haptens; Humans; Immunohistochemistry; Prognosis; Retrospective Studies; Chi-Square Distribution; In Situ Hybridization; Genes, erbB-2
  2. Heng PY, Sulong A, Ali UKS, Wong KK
    Malays J Pathol, 2019 Aug;41(2):139-148.
    PMID: 31427549
    INTRODUCTION: OXA-48, a carbapenem-hydrolysing class D β-lactamase, and its variant, OXA-181, are increasingly reported worldwide. This study aimed to describe the prevalence and distribution of OXA-48 and OXA-181 carbapenem-resistant Enterobacteriaceae (CRE) in a tertiary medical centre in Malaysia.

    MATERIALS & METHODS: A total of 13,098 Enterobacteriaceae isolates from various clinical samples were sent to our laboratory between January 2011 and December 2012. Of these, 90 demonstrated reduced susceptibility to at least one carbapenem and were included in this study. Only 88 isolates were successfully subcultured on blood agar (BA). Another 2 isolates failed to grow and were excluded. Of the 88, 2 isolates had the same identification number (repetitive isolates); therefore, 1 isolate was excluded from further analyses. Only 87 isolates were subjected to molecular detection of the blaOXA-48 and blaOXA-181 genes by polymerase chain reaction.

    RESULTS: Eighty-seven non-repetitive isolates grew following subculture on BA. Of these, 9 (10.34%) were positive for OXA-48 (7 Klebsiella pneumoniae, 2 Escherichia coli). Each isolate originated from different patients. All patients had a history of treatment with at least one cephalosporin and/or carbapenem prior to the isolation of OXA-48 CRE. OXA-181 was detected in one (1.15%) out of the 87 isolates; CONCLUSIONS: The prevalence of OXA-48 and OXA-181 CRE among all Enterobacteriaceae isolates in our institution is 0.069% and 0.008%, respectively. Nevertheless, our findings suggest that OXA-48 and OXA-181 carbapenemases appear to be important and possibly under-recognised causes of carbapenem resistance in Malaysia.

    MeSH terms: Agar; Bacterial Proteins; beta-Lactamases; Cephalosporins; Enterobacteriaceae; Escherichia coli; Humans; Klebsiella pneumoniae; Malaysia; Carbapenems; Prevalence; Polymerase Chain Reaction
  3. Haidary AM, Azma RZ, Ithnin A, Alauddin H, Tumian NR, Tamil AM, et al.
    Malays J Pathol, 2019 Aug;41(2):149-160.
    PMID: 31427550
    INTRODUCTION: BCR-ABL fusion gene, the oncogenic driver of CML, results from a translocation between short arms of chromosome 9 and 22. Monitoring of CML patients during treatment is essential, not only for tailoring the treatment but also to detect early relapse to enable timely intervention. Commonly used methods for detection of residual disease are conventional karyotyping, FISH and molecular methods. In this study, we compared FISH with QRT-PCR for detection of residual disease in CML.

    MATERIALS AND METHODS: CML patients on tyrosine kinase inhibitor (TKI) therapy and on regular follow up at University Kebangsaan Malaysia Medical Center (UKMMC) were selected. A comparative study was conducted between FISH and QRT-PCR for BCR-ABL transcripts at diagnosis and during follow-up.

    RESULTS: There was good correlation between FISH and QRT-PCR for BCR-ABL. At 6th month of follow-up post diagnosis, FISH had a sensitivity of 83.3% and specificity of 65.2% (k >0.339, p<0.033). At 12th month, the sensitivity of FISH was 83% and the specificity was 59.1% (k >0.286, p <0.065). Similarly, at the 24th month, FISH had a sensitivity of 100% and specificity of 68.8% (k >0.642, p<0.000).

    DISCUSSION: Early achievement of major molecular response (MMR) and complete cytogenetic remission (CCyR) were reliable predictors of long-term maintenance of molecular remission.

    MeSH terms: Chromosomes, Human, Pair 9; Follow-Up Studies; Humans; Karyotyping; Malaysia; Neoplasm Recurrence, Local; Translocation, Genetic; Universities; Fusion Proteins, bcr-abl; Polymerase Chain Reaction
  4. Tang YL, Yousuf R, Wan Nawawi WM, Rahman IL, Zainal Abidin J, Rechard Nathan VR, et al.
    Malays J Pathol, 2019 Aug;41(2):161-167.
    PMID: 31427551
    INTRODUCTION: Overnight transfusion (OT) is the blood transfusion taking place from 9pm to 8am. During this period, patients are exposed to increased risk of errors. This cross-sectional study aims to determine the incidence and practice of OT in Universiti Kebangsaan Malaysia Medical Centre.

    MATERIALS & METHODS: Data from all OT in June and mid-July 2017 were collected from recipients' cards, transfusion request forms and patient's case files, regarding discipline involved, indications, time intervals from request of blood transfusion to the completion of OT on patients, monitoring of patients and adverse reactions.

    RESULTS: A total of 1285 transfusion cases were identified during the study period. 216 (16.8%) cases were OT while the 1069 (83.2%) cases were non-OT. Surgery discipline has the highest (30.1%) OT. The indications of OT were acute clinical need: 82.9%, less acute clinical need: 13.9% and no clinical need: 3.2%. A huge delay (average: 5 hours 40 minutes) in starting transfusion after grouping and crossmatching (GXM) completion was noted. Besides, 25.9% cases took <4 hours to complete OT; 83.4% cases did not have proper transfusion monitoring and three transfusion reactions were reported.

    DISCUSSION: Although most of the OT cases had appropriate clinical indications, the transfusion can be commenced earlier at day time rather than overnight. Cases without absolute indication should avoid OT. The poor monitoring of patient during OT had posed risks to patients' life if an adverse transfusion reaction happened. The major reason for OTs was a huge delay in starting transfusion after the GXM completion. The contravention of 4-hour infusion rule increased the patients' risk of developing bacterial sepsis. The practice of OT should be discouraged wherever possible except for clinically indicated cases.

    MeSH terms: Blood Grouping and Crossmatching; Blood Transfusion; Cross-Sectional Studies; Humans; Malaysia; Incidence; Platelet Transfusion; Sepsis; Transfusion Reaction
  5. Mohd Ashari NS, Mohamed Sanusi SNF, Mohd Yasin MA, Che Hussin CM, Wong KK, Shafei MN
    Malays J Pathol, 2019 Aug;41(2):169-176.
    PMID: 31427552
    INTRODUCTION: Regulatory T cell (Treg) is a subtype of T lymphocyte that plays a crucial role in establishing immunologic self-tolerance and maintaining immune homeostasis. In this study, we set out to investigate the percentage and absolute count of Tregs in major depressive disorder (MDD) patients and their correlation with disease severity.

    MATERIALS & METHODS: This is a case-control study consisting of 47 MDD patients and 47 healthy controls. MDD patients were treated with antidepressant drugs according to their physician's choice. The severity of MDD was assessed using Beck Depression Inventory (BDI) and Montgomery-Asberg Depression Rating Scale (MADRS) at the time of recruitment. Healthy controls completed the Depression Anxiety Scoring System (DASS21) questionnaire to ensure they were in good mental health without history of MDD. The percentage and absolute count of CD4+ CD25+ Tregs and CD4+ CD25+ FOXP3+ Tregs were identified by multiparameter flow cytometry.

    RESULTS: The percentage and absolute count of CD4+ CD25+ Treg cells were significantly higher in MDD patients than in healthy controls (P<0.001, in both cases). Likewise, the percentage and absolute count of CD4+ CD25+ FOXP3+ Treg cells were also significantly higher in MDD patients compared to healthy controls (P=0.003 and P=0.002, respectively). However, there was no significant correlation between the percentage and absolute count of CD4+ CD25+ Treg and CD4+ CD25+ FOXP3+ Treg cells with BDI or MADRS score.

    CONCLUSIONS: Our results suggest that antidepressant treatments contributed to an upregulation of Tregs in MDD patients.

    MeSH terms: Antidepressive Agents; Anxiety; Depression; Depressive Disorder, Major; Flow Cytometry; Homeostasis; Humans; Mental Health; Surveys and Questionnaires; Up-Regulation; Case-Control Studies; Self Tolerance; T-Lymphocytes, Regulatory
  6. Kaur M, Rahimi R, Razali F, Mohd Noor N, Omar E, Abdul Manaf Z, et al.
    Malays J Pathol, 2019 Aug;41(2):177-183.
    PMID: 31427553
    INTRODUCTION: Coronary artery disease (CAD) is a known cause of major cardiovascular events and calcium score (CS) has been developed as a marker of coronary atherosclerosis. Yet, the relationship between post mortem computed tomography (PMCT) CS with histologically observed calcification and the severity of coronary artery stenosis has not been widely explored and is still unclear. This study aims to determine the association between coronary artery PMCT CS with histologically observed calcification and degree of stenosis of coronary arteries in post-mortem cases.

    MATERIALS & METHODS: This was a cross-sectional study involving 101 subjects recruited from the National Institute of Forensic Medicine (IPFN) Hospital Kuala Lumpur (HKL) over a period of 15 months, from December 2012 until April 2014. PMCT CS of the coronary arteries was calculated using Agatston-Janowitz score. Histological presence of calcification was observed and the degree of stenosis was calculated using an image analysis technique.

    RESULTS: PMCT CS increased with increasing severity of stenosis (p<0.001). PMCT CS showed a positive correlation with the presence of calcification (r=-0.82, p<0.001).

    CONCLUSION: Calcium score is strongly associated with coronary artery calcification and the degree of luminal stenosis in post mortem subjects. Thus, PMCT may be useful as a non-invasive tool in diagnosing CAD in the event that an autopsy is not possible.

    MeSH terms: Autopsy; Calcification, Physiologic; Calcinosis; Calcium; Constriction, Pathologic; Coronary Artery Disease; Cross-Sectional Studies; Tomography; Coronary Stenosis
  7. Wan Ab Rahman WS, Abdullah WZ, Husin A, Nik Mohd Hassan NFF, Hassan MN, Zulkafli Z
    Malays J Pathol, 2019 Aug;41(2):185-189.
    PMID: 31427554
    INTRODUCTION: Acquired haemophilia A (AHA) is a rare acquired bleeding disorder caused by polyclonal immunoglobulin G autoantibodies against clotting factor VIII (FVIII). The incidence was reported to be rare occurring in 0.2- 4 cases/million/year. Patients may present with different clinical manifestations to various specialties. Early recognition of the disease contributes to favourable clinical outcome.

    CASE SERIES: Here, we reported five cases of this disorder with different clinical presentations from two tertiary hospitals in Kelantan state, Malaysia within a two year-period. Most of them were elderly, except for one who presented at the age of 36 years old. No direct or secondary cause was identified except for one patient who had developed from pregnancy-related at 3 weeks postpartum. These patients presented with spontaneous bleeding typically into skin, muscles, and mucous membranes but also at rare site in the epidural space. All patients denied previous history of bleeding or family history of bleeding disorder. FVIII activities were recorded between <1% to 19%, while the inhibitor titre levels were between 3.9 BU to 340 BU. The treatment approaches especially at presentation were complicated by unfamiliarity of managing this rare condition but all these patients received appropriate medical attention.

    DISCUSSION: Prompt diagnosis and management in the right hand are critical. Awareness of this disorder by medical personnel at all levels in the community and in various specialties is important.

    MeSH terms: Aged; Attention; Autoantibodies; Epidural Space; Factor VIII; Female; Hemophilia A; Hemorrhage; Humans; Immunoglobulin G; Malaysia; Mucous Membrane; Pregnancy; Incidence; Postpartum Period; Tertiary Care Centers
  8. Sharma A, Ahuja S, Diwaker P, Wadhwa N, Arora VK
    Malays J Pathol, 2019 Aug;41(2):191-194.
    PMID: 31427555
    INTRODUCTION: Acinic cell carcinoma (ACC) represents 1-6% of parotid gland neoplasms.

    CASE REPORT: We report cytomorphological features of two uncommon variants of acinic cell carcinoma. The first case was an eleven-year-old female with a nodular mass in parotid and the FNA smears demonstrated a lymphoepithelial lesion composed of epithelial tumour cells with features of acinar cells in a lymphoid background. The second case was a 62-year-old male with a large parotid mass. The FNA smears revealed presence of extracellular, acellular amyloid-like material with tumour cells arranged in follicles.

    DISCUSSION: Awareness of cytomorphological features of these unusual variants of acinic cell carcinoma may help to avoid diagnostic pitfall.

    MeSH terms: Amyloid; Epithelial Cells; Female; Male; Parotid Gland; Parotid Neoplasms; Carcinoma, Acinar Cell; Amyloidogenic Proteins; Acinar Cells
  9. Wan Ahmad Kammal WS, Mohd Rose I, Md Zin RR, Raja Ali RA, Masir N
    Malays J Pathol, 2019 Aug;41(2):195-199.
    PMID: 31427556
    INTRODUCTION: Extranodal NK/T cell lymphoma is a rare tumour, typically involving the upper aerodigestive tract. Even rarer is primary extranasal disease involving the skin, testis, soft tissue and gastrointestinal tract.

    CASE REPORT: We report a case of a 46-year-old Chinese male who presented with six months history of abdominal pain, weight loss and rectal bleeding. Diagnostic colonoscopy revealed multiple aphthous ulcers within the ileo-caecal region and distal transverse colon, separated by normal mucosa, mimicking skip lesions of Crohn's colitis. Computer topography (CT) scan of the abdomen showed multiple circumferential thickenings involving predominantly the right colon. A clinical diagnosis of colonic Crohn's disease with possible perforation was made. An extended right hemicolectomy was performed due to uncontrolled rectal bleeding. Histopathology examination of the colon showed infiltration by malignant lymphoid cells associated with necrosis, angiocentricity and angiodestruction. Immunohistochemical studies confirmed T-cell monoclonality, presence of cytotoxic granules and Epstein-Barr virus (EBV) infection. A diagnosis of extranodal NK/T cell lymphoma of the colon was made.

    DISCUSSION: These findings highlight that colonic NK/T cell lymphoma may clinically mimic other benign inflammatory lesions and should be one of the differential diagnoses in patients presenting with gastrointestinal lesions. The final diagnosis is only possible with appropriate histological and immunohistochemical studies.

    MeSH terms: Colectomy; Colitis; Colonoscopy; Crohn Disease; Diagnosis, Differential; Herpesvirus 4, Human; Humans; Male; Mucous Membrane; Stomatitis, Aphthous; T-Lymphocytes; Testis; Tomography, X-Ray Computed; Weight Loss; Abdominal Pain; Epstein-Barr Virus Infections; Abdominal Cavity; Colon, Transverse; Lymphoma, Extranodal NK-T-Cell
  10. Lee M, Son HJ, Kim NY, Kim SJ, Yu IK
    Malays J Pathol, 2019 Aug;41(2):201-206.
    PMID: 31427557
    We present a case of an undifferentiated subtype of non-keratinizing squamous cell carcinoma (NK-SCC) with sarcomatoid features in the nasopharynx in a 69-year-old man who was difficult to diagnose due to spindle-shaped malignant cells. He was admitted because of a right nasal obstruction and right headache, and imaging revealed a heterogeneously enhanced irregularly shaped mass at the nasopharynx. Histopathologically, the tumour was partially organised, and the tumour cells were epithelioid or spindle-shaped. Initially, we erroneously diagnosed the tumour as an angiosarcoma owing to its false-negative immunoreaction for cytokeratins and a mistaken interpretation for CD31. After in situ hybridization for Epstein-Barr virus was positive, a consultation and additional immunostaining (including re-staining for cytokeratin with varying dilutions) were performed, and the diagnosis was revised to NK-SCC with sarcomatoid features. We believe that sarcomatoid features may be observed in nasopharyngeal carcinoma and in this case, immunostaining using various epithelial markers is necessary and careful attention should be paid to the interpretation of immunostaining.
    MeSH terms: Aged; Attention; Carcinoma, Squamous Cell; Herpesvirus 4, Human; Headache; Hemangiosarcoma; Humans; Keratins; Male; Nasopharyngeal Neoplasms; Referral and Consultation; Nasal Obstruction; In Situ Hybridization
  11. Lin SC, Ko RT, Kang BH, Wang JS
    Malays J Pathol, 2019 Aug;41(2):207-211.
    PMID: 31427558
    INTRODUCTION: Salivary gland intraductal carcinoma (IDC) is rare. We present the second case of IDC originating from an intraparotid lymph node (LN) with a more detailed description of the histogenesis, immunohistochemistry (IHC) and updated molecular information.

    CASE REPORT: An 87-year-old male had a tumour nodule over the left parotid tail for about 20 years. Physical examinations revealed a 4.5 cm soft, non-tender and fixed mass. After the left parotidectomy, pathology confirmed the diagnosis of IDC arising within an intraparotid lymph node. The cystic component of the tumour was lined by single to multilayered ductal cells with micropapillary growth pattern. The solid part showed intraductal proliferation of neoplastic cells in solid, cribriform, micropapillary and Roman bridge-like structure. By immunohistochemistry (IHC), the tumour cells were positive for S-100, CK (AE1/AE3), mammaglobin, SOX10, and estrogen receptor (ER), with myoepithelial cell rimming highlighted by positive p63 and calponin IHC stains. The prognosis of this patient is excellent after complete excision.

    DISCUSSION: The mechanism of salivary gland tumour arising in the intra-parotid gland LN was assumed to be related to salivary duct inclusion within the intraparotid gland LN which is a normal occurrence during embryology development. Although the terminology may raise some confusion about the relationship between IDC and conventional salivary duct carcinoma (SDA), they are different in immunophenotype and clinicopathologic features. IDC is characterised by S100 (+) ER (+) with predominant intraductal growth and excellent prognosis; while SDC features S100 (-) androgen receptor (+) with predominant invasive growth and aggressive behavior. Recent discovery of recurrent RET gene rearrangement in IDC but not SDC also supports that IDC is not precursor lesion of the SDC.

    MeSH terms: Aged, 80 and over; Calcium-Binding Proteins; Carcinoma, Intraductal, Noninfiltrating; Coloring Agents; Humans; Immunohistochemistry; Lymph Nodes; Male; Microfilament Proteins; Parotid Gland; Physical Examination; Prognosis; Receptors, Androgen; Receptors, Estrogen; Salivary Gland Neoplasms; Gene Rearrangement; Salivary Ducts; Carcinoma, Ductal; Cell Proliferation
  12. Lee JS, Choi SJ, Kim L, Park IS, Han JY, Kim JM, et al.
    Malays J Pathol, 2019 Aug;41(2):213-222.
    PMID: 31427559
    INTRODUCTION: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)-pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions.

    CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered.

    DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

    MeSH terms: Adult; Back Pain; Biopsy; Biopsy, Needle; Endoscopy; Female; Humans; Immunohistochemistry; Lymph Nodes; Lymphoma; Retrospective Studies; Lymphoma, Large-Cell, Anaplastic; Receptor Protein-Tyrosine Kinases; Cell Proliferation; Fractures, Compression; Pathologists
  13. Marsilla MM, Khairunisa AA, Azyani Y, Petrick P
    Malays J Pathol, 2019 Aug;41(2):223-227.
    PMID: 31427560
    INTRODUCTION: Histoplasmosis can present in a myriad of clinical manifestations, which often makes its diagnosis difficult and occasionally, deceptive.

    CASE REPORT: We describe a case of a 33 years old gentleman who was clinically diagnosed as acute appendicitis at initial presentation in view of a one-week history of fever, right lower quadrant abdominal pain- and guarding at right iliac fossa. He had thrombocytopenia and lymphopenia on presentation. Mesenteric lymphadenitis and small bowel lesion were found intraoperatively, which was respectively biopsied and resected. Histopathological result confirms disseminated histoplasmosis. Retroviral screen was positive. He was treated with amphotericin B for one week, subsequently switched to oral itraconazole, followed by initiation of highly active antiretroviral therapy (HAART).

    DISCUSSION: This case illustrates the various nature of histoplasmosis presentation. A high index of suspicion is needed to clinch the diagnosis and subsequently institute prompt treatment as disseminated disease can be fatal if left untreated in an immunosuppressed host.

    MeSH terms: Acute Disease; Amphotericin B; Appendicitis; Fever; Histoplasmosis; Ilium; Intestines; Lymphopenia; Male; Mesenteric Lymphadenitis; Thrombocytopenia; Abdominal Pain; Immunocompromised Host; Itraconazole; Antiretroviral Therapy, Highly Active
  14. Dhanuka S, Rodrigues G, Carnello S
    Malays J Pathol, 2019 Aug;41(2):229-232.
    PMID: 31427561
    INTRODUCTION: Palisaded encapsulated neuroma (PEN) is a benign lesion of Schwann cells and its occurrence in the oral mucosa especially the tongue is very rare.

    CASE REPORT: This article describes a case of a 41-year-old male, a chronic smoker with an actively bleeding, ulcerated, solitary, firm lesion on the lateral border of the tongue which had bled thrice before. A differential diagnosis of pyogenic granuloma, haemangioma, fibroma, nerve sheath tumour, salivary gland tumour and malignancy was made and surgically excised. Histopathology of the excised specimen revealed a well-circumscribed lesion with spindle-shaped cells arranged in interlacing fascicles and with the help of immunohistochemical markers confirmed it to be a PEN.

    DISCUSSION: To our knowledge, this is the first description of an ulcerated PEN presented with an active bleed.

    MeSH terms: Diagnosis, Differential; Fibroma; Hemangioma; Male; Mouth Mucosa; Neuroma; Salivary Glands; Schwann Cells; Granuloma, Pyogenic; Nerve Sheath Neoplasms
  15. Yong CY, Ong HK, Yeap SK, Ho KL, Tan WS
    Front Microbiol, 2019;10:1781.
    PMID: 31428074 DOI: 10.3389/fmicb.2019.01781
    Middle East respiratory syndrome (MERS) is a deadly viral respiratory disease caused by MERS-coronavirus (MERS-CoV) infection. To date, there is no specific treatment proven effective against this viral disease. In addition, no vaccine has been licensed to prevent MERS-CoV infection thus far. Therefore, our current review focuses on the most recent studies in search of an effective MERS vaccine. Overall, vaccine candidates against MERS-CoV are mainly based upon the viral spike (S) protein, due to its vital role in the viral infectivity, although several studies focused on other viral proteins such as the nucleocapsid (N) protein, envelope (E) protein, and non-structural protein 16 (NSP16) have also been reported. In general, the potential vaccine candidates can be classified into six types: viral vector-based vaccine, DNA vaccine, subunit vaccine, nanoparticle-based vaccine, inactivated-whole virus vaccine and live-attenuated vaccine, which are discussed in detail. Besides, the immune responses and potential antibody dependent enhancement of MERS-CoV infection are extensively reviewed. In addition, animal models used to study MERS-CoV and evaluate the vaccine candidates are discussed intensively.
  16. Zainul Azlan N, Mohd Yusof YA, Alias E, Makpol S
    PMID: 31428175 DOI: 10.1155/2019/8394648
    Background: Loss of skeletal muscle mass, strength, and function due to gradual decline in the regeneration of skeletal muscle fibers was observed with advancing age. This condition is known as sarcopenia. Myogenic regulatory factors (MRFs) are essential in muscle regeneration as its activation leads to the differentiation of myoblasts to myofibers. Chlorella vulgaris is a coccoid green eukaryotic microalga that contains highly nutritious substances and has been reported for its pharmaceutical effects. The aim of this study was to determine the effect of C. vulgaris on the regulation of MRFs and myomiRs expression in young and senescent myoblasts during differentiation in vitro.

    Methods: Human skeletal muscle myoblast (HSMM) cells were cultured and serial passaging was carried out to obtain young and senescent cells. The cells were then treated with C. vulgaris followed by differentiation induction. The expression of Pax7, MyoD1, Myf5, MEF2C, IGF1R, MYOG, TNNT1, PTEN, and MYH2 genes and miR-133b, miR-206, and miR-486 was determined in untreated and C. vulgaris-treated myoblasts on Days 0, 1, 3, 5, and 7 of differentiation.

    Results: The expression of Pax7, MyoD1, Myf5, MEF2C, IGF1R, MYOG, TNNT1, and PTEN in control senescent myoblasts was significantly decreased on Day 0 of differentiation (p<0.05). Treatment with C. vulgaris upregulated Pax7, Myf5, MEF2C, IGF1R, MYOG, and PTEN in senescent myoblasts (p<0.05) and upregulated Pax7 and MYOG in young myoblasts (p<0.05). The expression of MyoD1 and Myf5 in young myoblasts however was significantly decreased on Day 0 of differentiation (p<0.05). During differentiation, the expression of these genes was increased with C. vulgaris treatment. Further analysis on myomiRs expression showed that miR-133b, miR-206, and miR-486 were significantly downregulated in senescent myoblasts on Day 0 of differentiation which was upregulated by C. vulgaris treatment (p<0.05). During differentiation, the expression of miR-133b and miR-206 was significantly increased with C. vulgaris treatment in both young and senescent myoblasts (p<0.05). However, no significant change was observed on the expression of miR-486 with C. vulgaris treatment.

    Conclusions: C. vulgaris demonstrated the modulatory effects on the expression of MRFs and myomiRs during proliferation and differentiation of myoblasts in culture. These findings may indicate the beneficial effect of C. vulgaris in muscle regeneration during ageing thus may prevent sarcopenia in the elderly.

    MeSH terms: Aging; Cell Differentiation; Pharmaceutical Preparations; Humans; Regeneration; Myogenic Regulatory Factors; Muscle, Skeletal; Muscle Fibers, Skeletal; Myoblasts; MicroRNAs; Chlorella vulgaris; Cell Proliferation; PAX7 Transcription Factor; Sarcopenia; Eukaryota; Microalgae
  17. Chinnappan SM, George A, Thaggikuppe Krishnamurthy P, Choudhary Y, Choudhary VK, Ramani Y, et al.
    Evid Based Complement Alternat Med, 2019 07 21;2019:9186747.
    PMID: 31428177 DOI: 10.1155/2019/9186747
    [This corrects the article DOI: 10.1155/2019/4916519.].
    MeSH terms: Humans
  18. Browne N, Braoun C, McIlwain J, Nagarajan R, Zinke J
    PeerJ, 2019;7:e7382.
    PMID: 31428541 DOI: 10.7717/peerj.7382
    For reefs in South East Asia the synergistic effects of rapid land development, insufficient environmental policies and a lack of enforcement has led to poor water quality and compromised coral health from increased sediment and pollution. Those inshore turbid coral reefs, subject to significant sediment inputs, may also inherit some resilience to the effects of thermal stress and coral bleaching. We studied the inshore turbid reefs near Miri, in northwest Borneo through a comprehensive assessment of coral cover and health in addition to quantifying sediment-related parameters. Although Miri's Reefs had comparatively low coral species diversity, dominated by massive and encrusting forms of Diploastrea, Porites, Montipora, Favites, Dipsastrea and Pachyseris, they were characterized by a healthy cover ranging from 22 to 39%. We found a strong inshore to offshore gradient in hard coral cover, diversity and community composition as a direct result of spatial differences in sediment at distances <10 km. As well as distance to shore, we included other environmental variables like reef depth and sediment trap accumulation and particle size that explained 62.5% of variation in benthic composition among sites. Miri's reefs showed little evidence of coral disease and relatively low prevalence of compromised health signs including bleaching (6.7%), bioerosion (6.6%), pigmentation response (2.2%), scars (1.1%) and excessive mucus production (0.5%). Tagged colonies of Diploastrea and Pachyseris suffering partial bleaching in 2016 had fully (90-100%) recovered the following year. There were, however, seasonal differences in bioerosion rates, which increased five-fold after the 2017 wet season. Differences in measures of coral physiology, like that of symbiont density and chlorophyll a for Montipora, Pachyseris and Acropora, were not detected among sites. We conclude that Miri's reefs may be in a temporally stable state given minimal recently dead coral and a limited decline in coral cover over the last two decades. This study provides further evidence that turbid coral reefs exposed to seasonally elevated sediment loads can exhibit relatively high coral cover and be resilient to disease and elevated sea surface temperatures.
    MeSH terms: Animals; Borneo; Chlorophyll; Cicatrix; Mucus; Particle Size; Pigmentation; Seasons; Temperature; Prevalence; Anthozoa; Coral Reefs; Environmental Policy; Water Quality; Tartrate-Resistant Acid Phosphatase
  19. Othuman Mydin MA, Zamzani NM, Ghani ANA
    Data Brief, 2019 Aug;25:104320.
    PMID: 31428668 DOI: 10.1016/j.dib.2019.104320
    Quantifying the elevated temperature strengths of cement-based material is crucial to the design of building structural systems for fire resistance purpose. This paper collates a database of elevated temperature axial compressive and flexural strengths of coir fibre reinforced foamed concrete exposed to heating temperatures of 105 °C, 200 °C, 300 °C, 400 °C, 500 °C, 600 °C, 700 °C and 800 °C. There were four densities of foamed concrete of 700, 1100, 1500 and 1900 kg/m3 were prepared and tested. The untreated coir fibre was added in foamed concrete in percentages of 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% by mix volume fraction. The database can aid in prediction of elevated temperature strengths of fibre reinforced foamed concrete which can be exploited to assist manufacturers to develop their products without having to perform numerous large-scale elevated temperature tests in the future.
    MeSH terms: Dietary Fiber; Fires; Heating; Lignin; Paper; Temperature
  20. Li A, Geyer FC, Blecua P, Lee JY, Selenica P, Brown DN, et al.
    NPJ Breast Cancer, 2019;5:23.
    PMID: 31428676 DOI: 10.1038/s41523-019-0115-9
    Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.
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