Impact of elevated IgE in protective immunity and immunopathology of dengue.

Dengue is a mosquito-transmitted infection endemic in tropical and subtropical locations of the world where nearly half of the world's population resides. The disease may present as mild febrile illness to severe and can even be fatal if untreated. There are four genetically related but antigenically distinct dengue virus (DENV) serotypes. Immune responses to DENV infection are in general protective but under certain conditions, they can also aggravate the disease. The importance of the cellular immune responses and the antibody responses involving IgG and IgM has been well-studied. In contrast, not much has been described on the potential role of hypersensitivity reactions involving IgE in dengue. Several studies have shown elevated levels of IgE in patients with dengue fever, but its involvement in the immune response against the virus and disease is unknown. Activation of mast cells (MCs) and basophils mediated through dengue-specific IgE could result in the release of mediators affecting dengue virus infection. The present review explores the relationships between the induction of IgE in dengue virus infection, and the potential role of MCs and basophils, exploring both protective and pathogenic aspects, including antibody-dependent enhancement (ADE) of infection in dengue.

Development of a TaqMan minor groove binding probe-based quantitative reverse transcription polymerase chain reaction for the detection and quantification of Zika virus.

Zika virus (ZIKV) infection has emerged as a global health concern following epidemic outbreaks of severe neurological disorders reported in Pacific and Americas since 2016. Therefore, a rapid, sensitive and specific diagnostic test for ZIKV infection is critical for the appropriate patient management and the control of disease spread. A TaqMan minor groove binding (MGB) probe-based quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was developed based on the conserved sequence regions of 463 ZIKV NS2B genes. The designed ZIKV qRT-PCR assay was evaluated for its detection limit, strain coverage and cross-reactivity. We further assessed the clinical applicability of qRT-PCR assay for ZIKV RNA detection using a total 18 simulated clinical specimens. The detection limit of the qRT-PCR assay was 11.276 ZIKV RNA copies at the 95% probability level (probit analysis, p<= 0.05). Both Asian and African ZIKV strains were detected by the qRT-PCR assay without cross-reacting with DENV-1, DENV-2, DENV-3, DENV-4, CHIKV, JEV, LGTV, GETV and SINV. The qRT-PCR assay demonstrated a perfect agreement (k = 1.000, P < 0.001) with the reference assay; the sensitivity and specificity of the qRT-PCR assay were 100% (95% CI= 79.6-100) and 100% (95% CI= 43.9-100) respectively. The qRT-PCR assay developed in this study is a useful diagnostic tool for the broad coverage detection and quantification of both the Asian and African ZIKV strains.

Importance of Imaging in Congenital Unilateral Vocal Fold Paralysis: A Case of Neck Neuroblastoma Presenting with Unilateral Vocal Fold Paralysis.

Congenital vocal fold paralysis (VFP) is an important cause of respiratory compromise in infants. It can either be unilateral or bilateral, while imaging is routinely performed for bilateral VFP to evaluate for potential neurological causes, and such a practice may not be routine for unilateral VFP. While many of the unilateral VFP cases are idiopathic, the cause may occasionally be more sinister in nature, such as tumors. Therefore, unless an obvious cause of unilateral VFP is present (such as cardiac surgery or birth trauma), routine imaging of the brain, neck, and mediastinum should be performed for congenital unilateral VFP. We describe a rare case of a cervical neuroblastoma presenting with unilateral VFP that was detected only on imaging, thus highlighting its value and importance.

Hepatic Sarcoidosis: Diagnostic approach and management.

Sarcoidosis is a multi-systemic, non-caseating granulomatous disorder with an idiopathic aetiology. We report a 58-year-old Malay woman, with underlying type II diabetes mellitus, hypertension and history of stage II pulmonary sarcoidosis presenting with incidental finding of multiple hypodense liver lesions. Her recent contrasted enhanced computed tomography of the abdomen and pelvis demonstrated multiple intra-abdominal lymphadenopathies with evidence of liver and splenic infiltrations. Her ageappropriate malignancy screening was negative while liver biopsy showed non-caseating granulomatous hepatitis consistent with hepatic sarcoidosis. In view of her normal liver enzymes and normalised serum calcium levels, no immunosuppressive therapy was commenced. She remains asymptomatic and is currently under our close monitoring.

Multiplex sequencing of SARS-Cov-2 genome directly from clinical samples using the Ion Personal Genome Machine (PGM).

Various methods have been developed for rapid and high throughput full genome sequencing of SARS-CoV-2. Here, we described a protocol for targeted multiplex full genome sequencing of SARS-CoV-2 genomic RNA directly extracted from human nasopharyngeal swabs using the Ion Personal Genome Machine (PGM). This protocol involves concomitant amplification of 237 gene fragments encompassing the SARS-CoV-2 genome to increase the abundance and yield of viral specific sequencing reads. Five complete and one near-complete genome sequences of SARS-CoV-2 were generated with a single Ion PGM sequencing run. The sequence coverage analysis revealed two amplicons (positions 13 751-13 965 and 23 941-24 106), which consistently gave low sequencing read coverage in all isolates except 4Apr20-64- Hu. We analyzed the potential primer binding sites within these low covered regions and noted that the 4Apr20-64-Hu possess C at positions 13 730 and 23 929, whereas the other isolates possess T at these positions. The genome nucleotide variations observed suggest that the naturally occurring variations present in the actively circulating SARS-CoV-2 strains affected the performance of the target enrichment panel of the Ion AmpliSeq™ SARS CoV 2 Research Panel. The possible impact of other genome nucleotide variations warrants further investigation, and an improved version of the Ion AmpliSeq™ SARS CoV 2 Research Panel, hence, should be considered.

Evaluation of commercial serological assays in Malaysia for detection of anti-Zika virus antibodies.

The recommended test guidelines for Zika virus (ZIKV) include using both molecular and serological tools. While the molecular tools are useful for detecting acute infection, the serological tools are useful for the detection of previous infections. Nevertheless, detection of ZIKV-specific antibodies remains a challenge due to the high cross-reactivity between ZIKV and other flaviviruses such as dengue virus (DENV) and Japanese encephalitis virus (JEV). The objective of this study is to evaluate the commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of ZIKV IgG. In this study, we evaluated 6 commercially available anti-ZIKV IgG ELISA kits. Pre-characterized serum panels consisting of 70 sera were selected for the evaluation. The diagnostic accuracy of each ELISA kits was determined and compared to the gold standard, Foci Reduction Neutralization Test (FRNT). The present study established that the performance of the NS1-based anti-ZIKV IgG ELISA kit was superior to that which uses of the E protein as antigen. Overall, commercial ZIKV IgG ELISA showed varying test performances, with some achieving moderate to high test sensitivities and specificities. When compared against the FRNT, the test sensitivities ranged from 7.1% to 78.6%, whereas, the test specificities ranged from 40.0% to 100%. Limitation to the study includes the cross reactivity between flavivirus and specificity of the kit in addressing the cross reactivity.

Differential heterologous neutralisation profile against strains within DENV-3 genotype II.

The dengue virus type 3 (DENV-3) homotypic outbreak cycles reported in Klang Valley, Malaysia in 1992-1995 and 2002 demonstrated different epidemic magnitude and duration. These outbreak cycles were caused by two closely related strains of viruses within the DENV-3 genotype II (DENV-3/II). The role of viral genotypic diversity and factors that could have influenced this phenomenon were investigated. The serum neutralisation sensitivity of DEN3/II strains responsible for the DENV-3 outbreak cycles in 1992-1995 and 2002 were examined. Representative virus isolates from the respective outbreaks were subjected to virus neutralisation assay using identified sera of patients with homotypic (DENV-3) or heterotypic dengue infections (DENV-1 and DENV-2). Results from the study suggested that isolates representing DENV-3/II group E (DENV-3/II-E) from the 1992-1995 outbreak and DENV-3/II group F (DENV-3/II-F) from the 2002 outbreak were neutralised at similar capacity (intergenotypic differences <2-fold) by sera of patients infected with DENV-3, DENV-1 and DENV-2/Asian genotypes. Sera of the DENV-2/Cosmopolitan infection efficiently neutralised DENV-3/II-F (FRNT50 = 508.0) at a similar neutralisation capacity against its own homotypic serotype, DENV-2 (FRNT50 = 452.5), but not against DENV-3/II-E (FRNT50 = 100.8). The different neutralisation sensitivities of DENV-3/II strains towards the cross-reacting DENV-2 heterotypic immunity could play a role in shaping the DENV-3 recurring outbreaks pattern in Malaysia. Two genetic variations, E-132 (H/Y) and E-479 (A/V) were identified on the envelope protein of DENV-3/II-E and DENV-3/II-F, respectively. The E-132 variation was predicted to affect the protein stability. A more extensive study, however, on the implication of the naturally occurring genetic variations within closely related DENV genotypes on the neutralisation profile and protective immunity would be needed for a better understanding of the DENV spread pattern in a hyperendemic setting.

Multiplex sequencing of SARS-Cov-2 genome directly from clinical samples using the Ion Personal Genome Machine (PGM)

@#Various methods have been developed for rapid and high throughput full genome sequencing of SARS-CoV-2. Here, we described a protocol for targeted multiplex full genome sequencing of SARS-CoV-2 genomic RNA directly extracted from human nasopharyngeal swabs using the Ion Personal Genome Machine (PGM). This protocol involves concomitant amplification of 237 gene fragments encompassing the SARS-CoV-2 genome to increase the abundance and yield of viral specific sequencing reads. Five complete and one near-complete genome sequences of SARS-CoV-2 were generated with a single Ion PGM sequencing run. The sequence coverage analysis revealed two amplicons (positions 13 751-13 965 and 23 941-24 106), which consistently gave low sequencing read coverage in all isolates except 4Apr20-64Hu. We analyzed the potential primer binding sites within these low covered regions and noted that the 4Apr20-64-Hu possess C at positions 13 730 and 23 929, whereas the other isolates possess T at these positions. The genome nucleotide variations observed suggest that the naturally occurring variations present in the actively circulating SARS-CoV-2 strains affected the performance of the target enrichment panel of the Ion AmpliSeq™ SARS CoV 2 Research Panel. The possible impact of other genome nucleotide variations warrants further investigation, and an improved version of the Ion AmpliSeq™ SARS CoV 2 Research Panel, hence, should be considered.

Evaluation of commercial serological assays in Malaysia for detection of anti-Zika virus antibodies

@#The recommended test guidelines for Zika virus (ZIKV) include using both molecular and serological tools. While the molecular tools are useful for detecting acute infection, the serological tools are useful for the detection of previous infections. Nevertheless, detection of ZIKV-specific antibodies remains a challenge due to the high cross-reactivity between ZIKV and other flaviviruses such as dengue virus (DENV) and Japanese encephalitis virus (JEV). The objective of this study is to evaluate the commercially available enzyme-linked immunosorbent assay (ELISA) for the detection of ZIKV IgG. In this study, we evaluated 6 commercially available anti-ZIKV IgG ELISA kits. Pre-characterized serum panels consisting of 70 sera were selected for the evaluation. The diagnostic accuracy of each ELISA kits was determined and compared to the gold standard, Foci Reduction Neutralization Test (FRNT). The present study established that the performance of the NS1-based anti-ZIKV IgG ELISA kit was superior to that which uses of the E protein as antigen. Overall, commercial ZIKV IgG ELISA showed varying test performances, with some achieving moderate to high test sensitivities and specificities. When compared against the FRNT, the test sensitivities ranged from 7.1% to 78.6%, whereas, the test specificities ranged from 40.0% to 100%. Limitation to the study includes the cross reactivity between flavivirus and specificity of the kit in addressing the cross reactivity.

Syringocystadenoma papilliferum arising in a naevus sebaceous.

Naevus sebaceus is a cutaneous hamartoma with the potential of developing into benign or malignant neoplasms. Syringocystadenoma papilliferum (SCAP) have been reported to originate from naevus sebaceus. SCAP is a rare, benign adnexal skin tumour of apocrine or eccrine type of differentiation which typically presents as a nodule or a plaque on the scalp or face. We report a case of syringocystadenoma papilliferum arising in an undiagnosed pre-existing naevus sebaceus in a 56-year-old female.

Autochthonous spread of DENV-3 genotype III in Malaysia mitigated by pre-existing homotypic and heterotypic immunity.

Dengue virus type 3 genotype III (DENV-3/III) is widely distributed in most dengue-endemic regions. It emerged in Malaysia in 2008 and autochthonously spread in the midst of endemic DENV-3/I circulation. The spread, however, was limited and the virus did not cause any major outbreak. Spatiotemporal distribution study of DENV-3 over the period between 2005 and 2011 revealed that dengue cases involving DENV-3/III occurred mostly in areas without pre-existing circulating DENV-3. Neutralisation assays performed using sera of patients with the respective infection showed that the DENV-3/III viruses can be effectively neutralised by sera of patients with DENV-3 infection (50% foci reduction neutralisation titres (FRNT50) > 1300). Sera of patients with DENV-1 infection (FRNT50 ⩾ 190), but not sera of patients with DENV-2 infection (FRNT50 ⩽ 50), were also able to neutralise the virus. These findings highlight the possibility that the pre-existing homotypic DENV-3 and the cross-reacting heterotypic DENV-1 antibody responses could play a role in mitigating a major outbreak involving DENV-3/III in the Klang Valley, Malaysia.

Diagnosis and Surgical Management of Congenital Intranasal Teratoma in a Newborn: A Rare Case Report.

Teratomas are the most common germ cell tumors of childhood. Head and neck teratomas, however, account for less than five percent of all teratomas. Considered rare at an incidence of 1 in 20,000 to 40,000 live births, they may occur in the cervical region, nasopharynx, brain, orbit, or oropharynx. Teratoma presenting as an isolated intranasal mass is extremely rare. In this report, we describe a case of a mature teratoma arising from the roof of the nasal cavity presenting as an isolated intranasal mass, the first of its kind from our literature review. The tumor was resected endoscopically with no recurrence detected.

Detection in Malaysia of a Borrelia sp. From Haemaphysalis hystricis (Ixodida: Ixodidae).

Spirochetes from the Borrelia genus are known to cause diseases in humans, namely Lyme disease and relapsing fever. These organisms are commonly transmitted to humans by arthropod vectors including ticks, mite, and lice. Here, we report the molecular detection of a Borrelia sp. from a Haemaphysalis hystricis Supino tick collected from wildlife in an Orang Asli settlement in Selangor, Malaysia. Phylogenetic analyses of partial 16s rRNA and flaB gene sequences revealed that the Borrelia sp. is closely related to the relapsing fever group borreliae, Borrelia lonestari, Borrelia miyamotoi, and Borrelia theileri, as well as a number of uncharacterized Borrelia sp. from ticks in Portugal and Japan. To our knowledge, this is the first report of a Borrelia sp. detected in H. hystricis, and in Malaysia. The zoonotic potential of this Borrelia sp. merits further investigation.

Parental preferences with regards to disclosure following adverse events occurring in relation to medication use or diagnosis in the care of their children - perspectives from Malaysia.

INTRODUCTION: Open disclosure is poorly understood in Malaysia but is an ethical and professional responsibility. The objectives of this study were to determine: (1) the perception of parents regarding the severity of medical error in relation to medication use or diagnosis; (2) the preference of parents for information following the medical error and its relation to severity; and (3) the preference of parents with regards to disciplinary action, reporting, and legal action. METHODS: We translated and contextualised a questionnaire developed from a previous study. The questionnaire consisted of four case vignettes that described the following: medication error with a lifelong complication; diagnostic error with a lifelong complication; diagnostic error without lifelong effect; and medication error without lifelong effect. Each case vignette was followed by a series of questions examining the subject's perception on the above areas. We also determined the content validity of the questionnaire. We invited parents of Malaysian children admitted to the paediatric wards of Tuanku Jaafar Hospital to participate in the study. RESULTS: One hundred and twenty-three parents participated in the study. The majority of parents wanted to be told regarding the event. As the severity of the case vignettes increased, the desire for information, remedial action, acknowledgement of responsibility, compensation, punishment, legal action, and reporting to a higher agency also increased. The findings did not have strong evidence of a relationship with subject's demographics. CONCLUSION: This study gives insights into previously unexplored perspectives and preferences of parents in Malaysia regarding open disclosure. It also highlights the opportunity for more research in this area with potentially broad applications.

Why not nursing? A systematic review of factors influencing career choice among healthcare students.

BACKGROUND: A global shortage of healthcare professionals calls for effective recruitment and retention strategies. The nursing profession faces greater staffing shortages compared with other healthcare professions. Identifying these factors for choosing a career in health care is an important step in structuring future nursing recruitment strategies. AIM: This systematic review examined the motivations for choosing a career in health care, then compared them to factors that influence the choice to pursue a career in nursing. METHODS: A literature search of the CINAHL, PubMed, Web of Science and Scopus databases for articles published between 2002 and 2013 was conducted. The search included studies that focused on factors influencing career choice among undergraduate medicine, dentistry, pharmacy and nursing students. RESULTS: A total of 29 papers were included in the review. The themes and subthemes that emerged from this review included: (1) intrinsic factors, including a desire to help others and a personal interest in health care, (2) extrinsic factors, such as financial remuneration, job security, professional prestige and job autonomy, (3) socio-demographic factors such as gender and socio-economic status, and (4) interpersonal factors, encompassing the influence of family and other professional individuals. DISCUSSION: Healthcare professionals were generally motivated by intrinsic factors. However, public perceptions of nursing as a low-paying and low-status job have significantly hindered the participants' choice to pursue it as a career. CONCLUSION AND IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY: Nursing institutions could provide more platforms to help school leavers better understand the nursing career. In turn, hospital administrators could invite parents to nursing career fairs, increase financial remuneration for nurses, and provide decision-making avenues aimed at recruiting and retaining more nurses.

The experience of older people living independently in Singapore.

BACKGROUND: Globally, older people are living independently either alone or with their spouse, population continues to age. In Singapore, some may live with an unrelated older person in a public rental apartment. In Asia, these older people are associated with increased risks of poor health and social isolation, have poorer social support and a poor quality of life. Few studies have explored why these older people choose such living arrangements, the challenges they encountered and what has helped or may help them overcome these challenges. AIM: To explore older people's experiences of living independently or with an unrelated older person. METHODS: This descriptive qualitative study involved face-to-face interviews with 25 informants, 65 years or older in Singapore. Thematic analysis was adopted. RESULTS: Five themes emerged: (1) making own choice--participants decided to live apart from their families, (2) contending with concerns--the availability of external resources for participants was shrinking, (3) coping with the available assistance--depending on available external resources from the community, (4) holding on to their values--participants rely on their internal resources to manage, and (5) preparing for the inevitable--participants were planning for their final years of life and for their death. CONCLUSION: Older people have such living arrangements for many reasons. They attain well-being and quality of life by devising strategies, tapping on their limited external resources and relying on their values to manage their diminishing resources and the foreseeable death. IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY: Understanding older people's experiences may help nurses and health professionals to develop health promotion programmes that support older people's everyday needs and help them to stay healthy. Public health policy must support older people to live in a safe environment near their extended family to reduce their need to relocate.

Successful endovascular embolisation of a jejunal artery aneurysm.

Jejunal artery aneurysms are rare, with only six cases reported in the literature to date. Endovascular embolisation of the jejunal artery is rarely performed. Herein, we report the case of a 57-year-old man who successfully underwent endovascular embolisation for bleeding caecal diverticulosis, during which a 9-mm fusiform jejunal artery aneurysm was incidentally diagnosed. Subsequently, the jejunal aneurysm was successfully embolised using Vortex coils.

Prevention is better than Cure.

No abstract available.

The extent of inflammation is a predictor for pouch-related complications in ileal pouches in patients with ulcerative or indeterminate colitis.

AIM: Limited data are available on the relationship between the histological features of the resected specimens in patients with ulcerative colitis (UC) or indeterminate colitis (IC) and the outcome of restorative proctocolectomy. The aim of our study was to determine if the histological features of the resected specimen in patients with UC and IC can predict ileal-pouch-related outcome. METHOD: A review of all patients who had a restorative proctocolectomy created following completion proctectomy or proctocolectomy for UC and IC was performed. RESULTS: Between 1992 and 2011, 142 patients (132 with UC and 10 with IC) were reviewed. After a median follow-up of 36 (3-149) months, 51 (35.9%) developed a pouch-related complication. Forty-two (29.7%) developed pouchitis while three (2.1%) developed a pouch-cutaneous fistula. Four (2.8%) had pouch failure, while stricture of the anastomosis was seen in three (2.1%) patients. The presence of extension of the inflammation into the muscularis propria of the resected specimen was associated with an increased risk of pouch-related complications (P = 0.01). The presence of submucosal oedema was also a significant risk factor (P = 0.03). CONCLUSION: The extension of inflammation into the muscularis propria appears to predict pouch-related complications following restorative proctocolectomy for UC or IC.