The nucleocapsid protein (NP) of Newcastle disease virus expressed in E. coli assembled as ring- and herringbone-like particles. In order to identify the contiguous NP sequence essential for assembly of these particles, 11 N- or C-terminally deleted NP mutants were constructed and their ability to self-assemble was tested. The results indicate that a large part of the NP N-terminal end, encompassing amino acids 1 to 375, is required for proper folding to form a herringbone-like structure. In contrast, the C-terminal end covering amino acids 376 to 489 was dispensable for the formation of herringbone-like particles. A region located between amino acids 375 to 439 may play a role in regulating the length of the herringbone-like particles. Mutants with amino acid deletions further from the C-terminal end (84, 98, 109 and 114 amino acids) tended to form longer particles compared to mutants with shorter deletions (25 and 49 amino acids).
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which is mainly characterized by progressive impairment in cognition, emotion, language and memory in older population. Considering the impact of AD, formulations of pharmaceutical drugs and cholinesterase inhibitors have been widely propagated, receiving endorsement by FDA as a form of AD treatment. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis but merely targeting the symptoms so as to improve a patient's cognitive outcome. Hence, a search for better disease-modifying alternatives is put into motion. Having a clear understanding of the neuroprotective mechanisms and diverse properties undertaken by specific genes, antibodies and nanoparticles is central towards designing novel therapeutic agents. In this review, we provide a brief introduction on the background of Alzheimer's disease, the biology of blood-brain barrier, along with the potentials and drawbacks associated with current therapeutic treatment avenues pertaining to gene therapy, immunotherapy and nanotherapy for better diagnosis and management of Alzheimer's disease.
Despite the availability of Newcastle disease (ND) vaccines for more than six decades, disease outbreaks continue to occur with huge economic consequences to the global poultry industry. The aim of this study is to develop a safe and effective inactivated vaccine based on a recently isolated Newcastle disease virus (NDV) strain IBS025/13 and evaluate its protective efficacy in chicken following challenge with a highly virulent genotype VII isolate. Firstly, high titre of IBS025/13 was exposed to various concentrations of binary ethylenimine (BEI) to determine the optimal conditions for complete inactivation of the virus. The inactivated virus was then prepared in form of a stable water-in-oil emulsion of black seed oil (BSO) or Freund's incomplete adjuvant (FIA) and used as vaccines in specific pathogen-free chicken. Efficacy of various vaccine preparations was also evaluated based on the ability of the vaccine to protect against clinical disease, mortality and virus shedding following challenge with highly virulent genotype\VII NDV isolate. The results indicate that exposure of NDV IBS025/13 to 10 mM of BEI for 21 h at 37 °C could completely inactivate the virus without tempering with the structural integrity of the viral hemagglutin-neuraminidase protein. More so, the inactivated vaccines adjuvanted with either BSO- or FIA-induced high hemagglutination inhibition antibody titre that protected the vaccinated birds against clinical disease and in some cases virus shedding, especially when used together with live attenuated vaccines. Thus, genotype VII-based NDV-inactivated vaccines formulated in BSO could substantially improve poultry disease control particularly when combined with live attenuated vaccines.
One-day-old chickens were transported from Australia to Malaysia and vaccinated orotracheally with an uninactivated vaccine prepared from avirulent Australian V4 strain of Newcastle disease virus (NDV). The vaccination regimes were as follows: group A, once, at 2 weeks old; group B, once, at 3 weeks old; group C, twice, at 2 and at 3 weeks old; group D, direct contact with groups A, B, and C; and group E, indirect contact with groups A, B, C, and D. Group F was unvaccinated controls. Challenge was with NDV virulent Ipoh AF 2240-226 strain, administered at 4 weeks old intramuscularly to 10 chickens in each group and orotracheally to 10 chickens in each group. The remaining chickens were challenged by contact with the inoculated chickens. Group mortalities following challenge were: A, 1/77; B, 1/34; C, 0/39; D, 0/45; E, 6/43; and F, 60/60.
The discovery of tumour selective virus-mediated apoptosis marked the birth of an alternative cancer treatment in the form of oncolytic viruses. Even though, its oncolytic efficiency was demonstrated more than 50 years ago, safety concerns which resulted from mild to lethal side effects hampered the progress of oncolytic virus research. Since the classical oncolytic virus studies rely heavily on its natural oncolytic ability, virus manipulation was limited, thereby, restricted efforts to improve its safety. In order to circumvent such restriction, experiments involving non-human viruses such as the avian Newcastle disease virus (NDV) was conducted using cultured cells, animal models and human subjects. The corresponding reports on its significant tumour cytotoxicity along with impressive safety profile initiated immense research interest in the field of oncolytic NDV. The varying degree of oncolytic efficiency and virulency among NDV strains encouraged researchers from all around the world to experiment with their respective local NDV isolates in order to develop an oncolytic virus with desirable characteristics. Such desirable features include high tumour-killing ability, selectivity and low systemic cytotoxicity. The Malaysian field outbreak isolate, NDV strain AF2240, also currently, receives significant research attention. Apart from its high cytotoxicity against tumour cells, this strain also provided fundamental insight into NDV-mediated apoptosis mechanism which involves Bax protein recruitment as well as death receptor engagement. Studies on its ability to selectively induce apoptosis in tumour cells also resulted in a proposed p38 MAPK/NF-κB/IκBα pathway. The immunogenicity of AF2240 was also investigated through PBMC stimulation and macrophage infection. In addition, the enhanced oncolytic ability of this strain under hypoxic condition signifies its dynamic tumour tropism. This review is aimed to introduce and discuss the aforementioned details of the oncolytic AF2240 strain along with its current challenges which outlines the future research direction of this virus.
Newcastle disease (ND) is one of the most devastating diseases that considerably cripple the global poultry industry. Because of its enormous socioeconomic importance and potential to rapidly spread to naïve birds in the vicinity, ND is included among the list of avian diseases that must be notified to the OIE immediately upon recognition. Currently, virus isolation followed by its serological or molecular identification is regarded as the gold standard method of ND diagnosis. However, this method is generally slow and requires specialised laboratory with biosafety containment facilities, making it of little relevance under epidemic situations where rapid diagnosis is seriously needed. Thus, molecular based diagnostics have evolved to overcome some of these difficulties, but the extensive genetic diversity of the virus ensures that isolates with mutations at the primer/probe binding sites escape detection using these assays. This diagnostic dilemma leads to the emergence of cutting-edge technologies such as next-generation sequencing (NGS) which have so far proven to be promising in terms of rapid, sensitive, and accurate recognition of virulent Newcastle disease virus (NDV) isolates even in mixed infections. As regards disease control strategies, conventional ND vaccines have stood the test of time by demonstrating track record of protective efficacy in the last 60 years. However, these vaccines are unable to block the replication and shedding of most of the currently circulating phylogenetically divergent virulent NDV isolates. Hence, rationally designed vaccines targeting the prevailing genotypes, the so-called genotype-matched vaccines, are highly needed to overcome these vaccination related challenges. Among the recently evolving technologies for the development of genotype-matched vaccines, reverse genetics-based live attenuated vaccines obviously appeared to be the most promising candidates. In this review, a comprehensive description of the current and emerging trends in the detection, identification, and control of ND in poultry are provided. The strengths and weaknesses of each of those techniques are also emphasised.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons. Motor features such as tremor, rigidity, bradykinesia and postural instability are common traits of PD. Current treatment options provide symptomatic relief to the condition but are unable to reverse disease progression. The conventional single-target therapeutic approach might not always induce the desired effect owing to the multifactorial nature of PD. Hence, multitarget strategies have been proposed to simultaneously target multiple proteins involved in the development of PD. Herein, we provide an overview of the pathogenesis of PD and the current pharmacotherapies. Furthermore, rationales and examples of multitarget approaches that have been tested in preclinical trials for the treatment of PD are also discussed.
A panel of six monoclonal antibodies (mAbs) against the nucleocapsid (NP) protein of Newcastle disease virus (NDV) was produced by immunization of Balb/c mice with purified recombinant NP protein. Western Blot analysis showed that all the mAbs recognized linearized NP epitopes. Three different NP antigenic sites were identified using deleted truncated NP mutants purified from Escherichia coli. One of the antigenic sites was located at the C-terminal end (residues 441 to 489) of the NP protein. Two other antigenic sites were located within the N-terminal end (residues 26-121 and 122-375). This study demonstrates that the N- and C-terminal ends of the NP proteins are responsible in eliciting immune response, thus it is most likely that these ends are exposed on the NP.
The new 64-row multidetector computed tomography (CT)-assisted angiography can now detect coronary artery disease with shorter breath-hold time and at faster heart rates for symptomatic patients. We aim to determine if the 64-row scanner can also overcome limitations due to mild to moderate calcification.
Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.
A case of Newcastle disease virus infection in a female laboratory technician is reported for the first time in Malaysia. Infection was acquired by droplet infection of the eye while grinding infected chicken in the laboratory. The case was confirmed by isolation of Newcastle disease virus from an eye swab taken from the subject on the first day of clinical signs. A four-fold rise of haemagglutination-inhibition titre was shown when sera on the third day of infection and 15 days later were compared.
Patients suffering from chronic diseases are more likely to experience pDDIs due to older age, prolonged treatment, severe illness and greater number of prescribed drugs. The objective of the current study was to assess the prevalence of pDDIs and risk factors associated with occurrence of pDDIs in chronic disease patients attending outpatient clinics for regular check-ups. Patients suffering from diabetes, chronic obstructive pulmonary disease (COPD), stroke and osteoporosis were included in the study. This study was a cross sectional, observational, prospective study that included 337 patients from outpatient clinics of respiratory ward, cardiac ward and orthopedic ward of Nishter Hospital Multan, Pakistan. The mean number of interactions per patient was 1.68. A greater risk for occurrence of pDDI was associated with older age ≥ 60 years (OR = 1.95, 95% CI = 1.44-2.37, p<0.001); polypharmacy (≥ 5 drugs) (OR = 3.74, 95% CI 2.32-4.54, p<0.001); overburden (OR = 2.23, 95% CI = 1.64-3.16, p<0.01); CCI score (OR = 1.28, 95% CI = 1.04-1.84, p<0.001); multiple prescribers to one patient (OR = 1.18, 95% CI = 1.06-1.41, p<0.01); and trainee practitioner (OR = 1.09, 95% CI = 1.01-1.28, p<0.01). Old age, polypharmacy, overburden healthcare system, higher comorbidity index, multiple prescribers to one patient and trainee practitioner were associated with increased risk of occurrence of pDDIs in chronic disease patients.
This study was aimed to investigate the possible association of Crohn's disease (CD) with inflammatory bowel disease gene 5 (IBD5) IGR2198a_1 (rs11739135), IGR2096a_1 (rs12521868) and interleukin-23 receptor (IL23R) genetic variant (rs1004819) in the Malaysian population.
Matched MeSH terms: Crohn Disease/genetics*; Genetic Predisposition to Disease
Hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth. The illness is caused by a number of enteroviruses with coxsackievirus A16 and enterovirus 71 as the main causative agents. Human enterovirus 71 (EV71) belongs to the species Human enterovirus A under the genus Enterovirus within the family Picornaviridae. EV71 has been associated with an array of clinical diseases including hand foot and mouth disease (HFMD), aseptic meningitis, encephalitis and poliomyelitis-like acute flaccid paralysis. A large outbreak of HFMD due to highly neurovirulent EV71 emerged in Malaysia in 1997, and caused 41 deaths amongst young children. In late 2000, a recurrence of an outbreak of HFMD occurred in Malaysia with 8 fatalities in peninsular Malaysia. Outbreak of HFMD due to EV71 recurred in 2003 with an unknown number of cases and mortalities. A similar outbreak of HFMD with 2 recorded deaths in young children occurred in peninsular Malaysia in late 2005 and this was followed by a larger outbreak in Sarawak (Malaysian Borneo) with 6 reported fatalities in the early part of 2006. The current on-going outbreak of HFMD started in peninsular Malaysia in epidemiological week 12 of 2010. As with other HFMD outbreaks in Malaysia, both EV71 and CA16 were the main aetiological viruses isolated. In similarity with the HFMD outbreak in 2005, the isolation of CA16 preceded the appearance of EV71. Based on the VP1 gene nucleotide sequences, 4 sub-genogroups of EV71 (C1, C2, B3 and B4) co-circulated and caused the outbreak of hand, foot and mouth disease in peninsular Malaysia in 1997. Two sub-genogroups (C1 and B4) were noted to cause the outbreak in 2000 in both peninsular Malaysia and Sarawak. EV71 of sub-genogroup B5 with smaller contribution from sub-genogroup C1 caused the outbreak in 2003. In the 2005 outbreak, besides the EV71 strains of sub-genogroup C1, EV71 strains belonging to sub-genogroup B5 were isolated but formed a cluster which was distinct from the EV71 strains from the sub-genogroup B5 isolated in 2003. The four EV71 strains isolated from clinical specimens of patients with hand, foot and mouth disease in the Sarawak outbreak in early 2006 also belonged to sub-genogroup B5. Phylogenetic analysis of the VP1 gene suggests that the EV71 strains causing the outbreak in Sarawak could have originated from peninsular Malaysia. Epidemiological and molecular data since 1997 show the recurrence of HFMD due to EV71 in Malaysia every 2 to 4 years. In each of the past outbreaks, more than one sub-genogroup of the virus co-circulate.
Matched MeSH terms: Hand, Foot and Mouth Disease/epidemiology*; Hand, Foot and Mouth Disease/virology*
Quality of life after acute coronary heart disease amongst patients is important outcome factor in deliberations of patient's care. The main aim of the study was to examine the quality of life amongst acute CHD patients.
We analysed the outcome of 104 patients from a single institution who underwent allogeneic haematopoietic stem cell transplantation (AHSCT) from their HLA-identical siblings between 1993 and 2006. Sixty-nine percent of patients had peripheral blood stem cell (PBSC) as the stem cell source and the remaining had bone marrow (BM). The majority of patients are Chinese (60%) followed by Malays (24%) and Indians (14%). The median time to reach white cell counts of >1 x 10(9)/L and platelet counts of >30 x 10(9)/L was 13 and 15 days, respectively in patients who had PBSC transplantation compared with 16 and 25 days in patients who had BM transplantation, (p < 0.0001 and p < 0.001). Acute graft-versus-host disease (aGVHD) of grade II to IV was observed in 34% of patients and chronic graft-versus-host disease (cGVHD) in 38% of patients. Although not statistically significant, there was a higher incidence of overall aGVHD in Indian patients (73%) compared to Chinese and Malays (57% and 56% respectively). There was no significant difference in the incidence of aGVHD and cGVHD with the source of stem cells. Overall survival (OS) and disease free survival (DFS) was 50% and 60% at five years respectively. Multivariate analysis showed that patients transplanted in standard risk and those who had limited cGVHD had a significant better OS, (p = 0.05 and p = 0.05). Patients who had cGVHD and transplanted in standard risk had a better DFS, (p = 0.002 and p < 0.001). In summary, AHSCT in standard risk patients is associated with a better outcome than those transplanted in high risk and although not statistically significant, there is a higher incidence of aGVHD in Indian patients.
Matched MeSH terms: Graft vs Host Disease/epidemiology; Disease-Free Survival
Many triggering factors for onset of emerging infectious diseases are now recognised, such as: globalisation, demographic increase, population movements, international trade, urbanisation, forest destruction, climate changes, loss in biodiversity, and extreme life conditions such as poverty, famine and war. Epidemic burden is often leading to disasters, in terms of human losses, as well as economic, political or social consequences. These outbreaks may jeopardize within a few weeks or months, industry, trade, or tourism. While dengue and its most severe forms (hemorrhagic and shock syndrome) is spreading all over the tropical world, another arbovirosis, chikungunya disease dramatically spread in Indian Ocean islands where 30 to 75% of population were infected in 2005 and 2006, and then extended its progression towards India, Sri Lanka, Indonesia, Malaysia, Maldives islands with more than a million people infected with the East-African strain, replacing the former Asian strain which was known to prevail more than 30 years ago in India. Patients experience sequelae with disability, work loss, and rarely severe outcome recently identified in La Réunion and Mayotte (French overseas territories). No country, no part of the world may consider itself as protected against such events. However, consequences of emerging or re-emerging diseases are more and more unacceptable when they impact the poorest countries of the world. Viruses, bacteria, as well as wild animals, birds, or arthropods are not stopped by borders. It is time now to promote barriers against infectious diseases, including prevention, anticipation, disease surveillance and research. This is not only for humanitarian reasons, but also for contributing to a sustainable development with equity for worldwide population. This report presents comprehensive actions taken in 2006 for tracing the epidemic and mobilise research, as requested to the task force set up by the Prime Minister by March 20, 2006.