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Serum IgA cross-reactivity between glycine-alanine repeat sequence of EBNA-1 and keratin or collagen in nasopharyngeal carcinoma

Mathew A, Cheng HM, Sam CK, Prasad U

Clin. Immunol. Immunopathol., 1994 May;71(2):164-8.
PMID: 7514112

Inhibition studies were carried out to study possible cross-reactivity between a peptide fragment of the Epstein-Barr virus nuclear antigen, EBNA-1, and keratin/collagen. The 20-amino acid peptide (pAG), derived from a glycine-alanine repeat region of EBNA-1, uniquely makes up about one-third of the viral protein and is a dominant IgA antigenic epitope in patients with nasopharyngeal carcinoma (NPC). A small percentage of normal human sera (NHS) also binds pAG and this reactivity is examined in this study. Ten percent (2/20) and 13.4% (2/15) of IgA-pAG-positive NPC sera and NHS, respectively, were significantly inhibited by keratin in a competitive ELISA system. Conversely, 31.6% (6/19) and 30.8% (4/13) of IgA-keratin-positive NPC sera and NHS, respectively, were significantly inhibited by pAG. This indicated minimum cross-reactivity between IgA serum antibodies to EBNA-1 and keratin. Using collagen as inhibitor, none of 18 and only 2/13 IgA-pAG-positive NPC sera and NHS, respectively, were inhibited. In the collagen ELISA system, only 2/19 (10.5%) and 4/25 (16%) of IgA-collagen-positive NPC sera and NHS, respectively, were inhibited with pAG. Therefore, cross-reactivity with collagen was also low. IgA-pAG-positive NHS may therefore not be a false positive phenomenon, but whether it may represent an early serological profile related to NPC carcinogenesis remains to be determined.
A high incidence of serum IgG antibodies to the Epstein-Barr virus replication activator protein in nasopharyngeal carcinoma

Mathew A, Cheng HM, Sam CK, Joab I, Prasad U, Cochet C

Cancer Immunol Immunother, 1994 Jan;38(1):68-70.
PMID: 8299121

The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.
Screening for nasopharyngeal carcinoma with an ELISA using the Epstein-Barr virus nuclear antigen, EBNA 1: a complementary test to the IgA/VCA immunofluorescence assay

Cheng HM, Foong YT, Mathew A, Sam CK, Dillner J, Prasad U

J Virol Methods, 1993 Apr;42(1):45-51.
PMID: 7686558

An ELISA using the Epstein-Barr virus nuclear antigen 1 (EBNA 1) was found to detect selectively specific IgA in sera from patients with nasopharyngeal carcinoma (NPC). The antigen, p107, was a 20-amino acid synthetic peptide, representing a major epitope of EBNA 1.267/294 (90.8%) of NPC patients had IgA antibodies to p107 but in normal individuals, only 41/577 (7.1%) had IgA/p107. In sera from patients with other cancers, 11/77 (14.3%) had IgA/p107 reactivity. 124 IgA/VCA positive and 86 IgA/VCA negative NPC sera were also tested for IgA/p107 binding in ELISA. The majority of IgA/VCA positive sera (117) also contained IgA/p107 antibodies. Of interest was the detection of 74/86 IgA/p107 reactive sera in the IgA/VCA negative group. The results suggest that the IgA/p107 ELISA could become a useful, complementary screening assay to the IgA/VCA immunofluorescence test for detection of NPC.
Fulltext Xerostomia - A Comprehensive Review with a Focus on Mid-Life Health

Jacob LE, Krishnan M, Mathew A, Mathew AL, Baby TK, Krishnan A

J Midlife Health, 2022;13(2):100-106.
PMID: 36276621 DOI: 10.4103/jmh.jmh_91_21

Xerostomia is defined as the subjective complaint of a dry mouth. Xerostomia is common in menopausal women owing to the hormonal changes which take place during midlife. Studies show a higher incidence of oral cancer in the postmenopausal period which substantiates the theory of estrogen deficiency in carcinogenesis. Radiotherapy in the treatment of these cancers can lead to oral dryness. Other etiological factors of xerostomia include systemic diseases commonly occurring in middle-aged individuals and xerogenic drugs. Saliva plays a pivotal role in the maintenance of oropharyngeal health and xerostomia can severely impair the quality of life. The aim of this review was to provide vital information pertaining to the etiology, signs, diagnosis, and treatment of xerostomia with an emphasis on midlife health. The articles for this review were obtained from PubMed Central, Google Scholar, EBSCO, Science Direct, Medknow, Scopus, EMBASE, Web of Science, and authorized textbooks published between 1988 and 2021.
Facile fabrication of arecanut palm sheath based robust hydrophobic cellulose nanopapers via self-assembly of ZnO nanoflakes and its shelf-life prediction for sustainable packaging applications

Poulose A, Mathew A, Uthaman A, Lal HM, Parameswaranpillai J, Mathiazhagan A, et al.

Int J Biol Macromol, 2024 Jan;255:128004.
PMID: 37979737 DOI: 10.1016/j.ijbiomac.2023.128004

Cellulose nanofibers have been extracted from arecanut palm sheath fibers via mild oxalic acid hydrolysis coupled with steam explosion technique. Cellulose nanofibers with diameter of 20.23 nm were obtained from arecanut palm sheath fibers. A series of robust hydrophobic cellulose nanopapers were fabricated by combining the synergistic effect of surface roughness induced by the successful deposition of zinc oxide (ZnO) nanoflakes and stearic acid modification via a simple and cost-effective method. In this work, agro-waste arecanut palm sheath was employed as a novel source for the extraction of cellulose nanofibers. 2 wt% of ZnO nanoflakes and 1 M concentration of stearic acid were used to fabricate mechanically robust hydrophobic cellulose nanopapers with a water contact angle (WCA) of 134°. During the deposition of zinc oxide nanoflakes on the CNP for inducing surface roughness, a hydrogen bonding interaction is formed between the hydroxyl groups of cellulose nanofibers and the zinc oxide nanoflakes. When this surface roughened CNP was dipped in stearic acid solution. The hydroxyl groups in zinc oxide nanoflakes undergoes esterification reaction with carboxyl groups in stearic acid solution forming an insoluble stearate layer and thus inducing hydrophobicity on CNP. The fabricated hydrophobic cellulose nanopaper displayed a tensile strength of 22.4 MPa and better UV blocking ability which is highly desirable for the sustainable packaging material in the current scenario. Furthermore, the service life of the pristine and modified cellulose nanopapers was predicted using the Arrhenius equation based on the tensile properties obtained during the accelerated ageing studies. The outcome of this study would be broadening the potential applications of hydrophobic and mechanically robust cellulose nanopapers in sustainable packaging applications.
Fulltext Clinical outcomes of abiraterone acetate and predictors of its treatment duration in metastatic castration-resistant prostate cancer: Real-world experience in the Southeast Asian cohort

Lim J, Amantakul A, Shariff N, Lojanapiwat B, Alip A, Ong TA, et al.

Cancer Med, 2020 Jul;9(13):4613-4621.
PMID: 32374087 DOI: 10.1002/cam4.3101

It is of much interest to understand the efficacy of abiraterone acetate (AA) in routine clinical practice. We assessed the clinical outcome of AA in patients with metastatic castration-resistant prostate cancer (mCRPC) and determined clinical factors associated with AA treatment duration in real-world setting. This real-world cohort consisted of 93 patients with mCRPC treated with AA in Thailand (58.1%) and Malaysia (41.9%). Primary endpoints were overall survival (OS) and biochemical progression-free survival (bPFS). Secondary endpoints were predictors associated with AA treatment duration evaluated with Cox proportional hazards regression. Around 74% were chemotherapy-naïve. The median AA treatment duration was 10 months (IQR 5.6-17.1). Malaysians had a relatively lower median OS and bPFS (OS 17.8 months; 95% CI 6.4-29.1, bPFS 10.4 months; 95% CI 8.8-12.0) compared to Thais (OS 27.0 months; 95% CI 11.3-42.7, bPFS 14.0 months; 95% CI 5.8-22.2), although it did not achieve statistical significance (P > .05). Patients with longer AA treatment duration (>10 months) had lower risk of death and longer bPFS, compared to those with shorter AA treatment duration (≤10 months) (hazard ratio [HR] 0.10, 95% CI 0.05-0.22 and HR 0.13, 95% CI 0.06-0.25, respectively). Multivariable analysis showed that PSA at AA initiation, presence of PSA response and chemotherapy-naive were independently associated with AA duration (P
Fulltext Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2

Aji G, Huang Y, Ng ML, Wang W, Lan T, Li M, et al.

Proc Natl Acad Sci U S A, 2020 09 29;117(39):24434-24442.
PMID: 32917816 DOI: 10.1073/pnas.2007856117

Sphingolipid dysregulation is often associated with insulin resistance, while the enzymes controlling sphingolipid metabolism are emerging as therapeutic targets for improving insulin sensitivity. We report herein that sphingosine kinase 2 (SphK2), a key enzyme in sphingolipid catabolism, plays a critical role in the regulation of hepatic insulin signaling and glucose homeostasis both in vitro and in vivo. Hepatocyte-specific Sphk2 knockout mice exhibit pronounced insulin resistance and glucose intolerance. Likewise, SphK2-deficient hepatocytes are resistant to insulin-induced activation of the phosphoinositide 3-kinase (PI3K)-Akt-FoxO1 pathway and elevated hepatic glucose production. Mechanistically, SphK2 deficiency leads to the accumulation of sphingosine that, in turn, suppresses hepatic insulin signaling by inhibiting PI3K activation in hepatocytes. Either reexpressing functional SphK2 or pharmacologically inhibiting sphingosine production restores insulin sensitivity in SphK2-deficient hepatocytes. In conclusion, the current study provides both experimental findings and mechanistic data showing that SphK2 and sphingosine in the liver are critical regulators of insulin sensitivity and glucose homeostasis.
International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2013-2018, Adult and Pediatric Units, Device-associated Module

Rosenthal VD, Duszynska W, Ider BE, Gurskis V, Al-Ruzzieh MA, Myatra SN, et al.

Am J Infect Control, 2021 Oct;49(10):1267-1274.
PMID: 33901588 DOI: 10.1016/j.ajic.2021.04.077

BACKGROUND: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific.
METHODS: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied.
RESULTS: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases.
CONCLUSIONS: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.