The incidence of Addison’s disease (AD) is rare. One of the most common causes of AD in developed countries is autoimmune. On the other hand, in developing countries, infective causes still predominate. The symptoms are mostly insidious in onset and non-specific, making it challenging to diagnose AD. The delay in starting the right treatment predisposes to high mortality due to Addison’s crisis. Hence, biochemical parameters play a vital role in diagnosing AD since they usually will present with prominent hyponatraemia, hyperkalaemia and hypoglycaemia. Here, we report a case of a 66-year-old man with multiple co-morbidities and disseminated histoplasmosis who pre- sented with asymptomatic hyponatraemia and hyperkalaemia and was eventually diagnosed with Addison’s disease. Although the non-specific symptoms from his multiple co-morbidities obscured the diagnosis of AD, comprehensive biochemical tests have helped in establishing the diagnosis.
Keros and Gera classifications are widely used to assess the risk of skull base injury during endoscopic sinus surgery. Although, both classifications are useful preoperatively to stratify risk of patients going for surgery, it is not practical to measure the respective lengths during surgery. In this study, we aimed to propose a new radiological classification (Thailand-Malaysia-Singapore (TMS)) to assess the anatomical risk of anterior skull base injury using the orbital floor (OF) as a reference. A total of 150 computed tomography images of paranasal sinuses (300 sides) were reviewed. The TMS classification was categorized into 3 types by measuring OF to cribriform plate and OF to ethmoid roof. Most patients were classified as TMS type 1, Keros type 2 and Gera class II, followed by patients classified as TMS type 3, Keros type 1 and Gera class 1. TMS has significant correlation with Keros classification (p
Adult immunization is a neglected and underpublicised issue in Southeast Asia. Vaccine-preventable diseases cause unnecessary morbidity and mortality among adults in the region, while inadequate immunization results in unnecessary costs, including those associated with hospitalization, treatment, and loss of income. Childhood vaccination coverage is high for the EPI diseases of diphtheria, tetanus and pertussis; however, unvaccinated, undervaccinated, and aging adults with waning immunity remain at risk from infection and may benefit from vaccination. Catch-up immunization is advisable for adults seronegative for hepatitis B virus, while immunization against the hepatitis A and varicella viruses may benefit those who remain susceptible. Among older adults, immunization against influenza and pneumococcal infections is likely to be beneficial in reducing morbidity and mortality. Certain vaccinations are also recommended for specific groups, such as rubella for women of child-bearing age, typhoid for those travelling to high-endemicity areas, and several vaccines for high-risk occupational groups such as health care workers. This paper presents an overview of a number of vaccine-preventable diseases which occur in adults, and highlights the importance of immunization to protect those at risk of infection.
This study examines the persistence of familial aggregation and familial predisposition to Ascaris lumbricoides and Trichuris trichiura infection over 2 periods of treatment and reinfection, in an urban community in Kuala Lumpur, Malaysia. Both parasite species were shown to be aggregated (assessed by the variance to mean ratio) within families at all 3 interventions, although no consistent trend in aggregation was observed over the period of the study. Associations between mean A. lumbricoides and T. trichiura infection levels of families, at all 3 interventions, were highly significant (P < 0.0001), suggesting persistent predisposition at the family level.
Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood-brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.
Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology.
In the present study, a nonlinear delayed coronavirus pandemic model is investigated in the human population. For study, we find the equilibria of susceptible-exposed-infected-quarantine-recovered model with delay term. The stability of the model is investigated using well-posedness, Routh Hurwitz criterion, Volterra Lyapunov function, and Lasalle invariance principle. The effect of the reproduction number on dynamics of disease is analyzed. If the reproduction number is less than one then the disease has been controlled. On the other hand, if the reproduction number is greater than one then the disease has become endemic in the population. The effect of the quarantine component on the reproduction number is also investigated. In the delayed analysis of the model, we investigated that transmission dynamics of the disease is dependent on delay terms which is also reflected in basic reproduction number. At the end, to depict the strength of the theoretical analysis of the model, computer simulations are presented.
Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.
Nipah virus (NiV; Paramyxoviridae) caused fatal encephalitis in humans during an outbreak in Malaysia in 1998/1999 after transmission from infected pigs. Our previous study demonstrated that the respiratory, lymphatic and central nervous systems are targets for virus replication in experimentally infected pigs. To continue the studies on pathogenesis of NiV in swine, six piglets were inoculated oronasally with 2.5 x 10(5) PFU per animal. Four pigs developed mild clinical signs, one exudative epidermitis, and one neurologic signs due to suppurative meningoencephalitis, and was euthanized at 11 days post-inoculation (dpi). Neutralizing antibodies reached in surviving animals titers around 1280 at 16 dpi. Nasal and oro-pharyngeal shedding of the NiV was detected between 2 and 17 dpi. Virus appeared to be cleared from the tissues of the infected animals by 23 dpi, with low amount of RNA detected in submandibular and bronchial lymph nodes of three pigs, and olfactory bulb of one animal. Despite the presence of neutralizing antibodies, virus was isolated from serum at 24 dpi, and the viral RNA was still detected in serum at 29 dpi. Our results indicate slower clearance of NiV from some of the infected pigs. Bacteria were detected in the cerebrospinal fluid of five NiV inoculated animals, with isolation of Streptococcus suis and Enterococcus faecalis. Staphylococcus hyicus was isolated from the skin lesions of the animal with exudative epidermitis. Along with the observed lymphoid depletion in the lymph nodes of all NiV-infected animals, and the demonstrated ability of NiV to infect porcine peripheral blood mononuclear cells in vitro, this finding warrants further investigation into a possible NiV-induced immunosuppression of the swine host.
Chili anthracnose is one of the most devastating fungal diseases affecting the quality and yield production of chili. The aim of this review is to summarize the current knowledge concerning the chili anthracnose disease, as well as to explore the use of marker-assisted breeding programs aimed at improving anthracnose disease resistance in this species. This disease is caused by the Colletotrichum species complex, and there have been ongoing screening methods of chili pepper genotypes with resistance to anthracnose in the field, as well as in laboratories. Conventional breeding involves phenotypic selection in the field, and it is more time-consuming compared to molecular breeding. The use of marker-assisted selection (MAS) on the basis of inheritance, the segregation ratio of resistance to susceptibility, and the gene-controlling resistance may contribute to the development of an improved chili variety and speed up the selection process, while also reducing genetic drag in the segregating population. More importantly, by using molecular markers, the linkage groups are determined dominantly and co-dominantly, meaning that the implementation of a reliable method to produce resistant varieties is crucial in future breeding programs. This updated information will offer a supportive direction for chili breeders to develop an anthracnose-resistant chili variety.
Infectious bursal disease is a highly contagious disease in the poultry industry and causes immunosuppression in chickens. Genome-wide regulations of immune response genes of inbred chickens with different genetic backgrounds, following very virulent infectious bursal disease virus (vvIBDV) infection are poorly characterized. Therefore, this study aims to analyse the bursal tissue transcriptome of six inbred chicken lines 6, 7, 15, N, O and P following infection with vvIBDV strain UK661 using strand-specific next-generation sequencing, by highlighting important genes and pathways involved in the infected chicken during peak infection at 3 days post-infection. All infected chickens succumbed to the infection without major variations among the different lines. However, based on the viral loads and bursal lesion scoring, lines P and 6 can be considered as the most susceptible lines, while lines 15 and N were regarded as the least affected lines. Transcriptome profiling of the bursa identified 4588 genes to be differentially expressed, with 2985 upregulated and 1642 downregulated genes, in which these genes were commonly or uniquely detected in all or several infected lines. Genes that were upregulated are primarily pro-inflammatory cytokines, chemokines and IFN-related. Various genes that are associated with B-cell functions and genes related to apoptosis were downregulated, together with the genes involved in p53 signalling. In conclusion, bursal transcriptome profiles of different inbred lines showed differential expressions of pro-inflammatory cytokines and chemokines, Th1 cytokines, JAK-STAT signalling genes, MAPK signalling genes, and their related pathways following vvIBDV infection.
Human saliva plays a pivotal role in digesting food and maintaining oral hygiene. The presence of electrolytes, mucus, glycoproteins, enzymes, antibacterial compounds, and gingival crevicular fluid in saliva ensures the optimum condition of oral cavity and general health condition. Saliva collection has been proven non-invasive, convenient, and inexpensive compared to conventional venipuncture procedure. These distinctive advantages provide a promising potential of saliva as a diagnostic fluid. Through comprehensive analysis, an array of salivary proteins and peptides may be beneficial as biomarkers in oral and systemic diseases. In this review, we discuss the utility of human salivary proteomes and tabulate the recent salivary biomarkers found in subjects with acute myocardial infarction as well as respective methods employed. In a clinical setting, since acute myocardial infarction contributes to large cases of mortality worldwide, an early intervention using these biomarkers will provide an effective solution to reduce global heart attack incidence particularly among its high-risk group of type-2 diabetes mellitus patients. The utility of salivary biomarkers will make the prediction of this cardiac event possible due to its reliability hence improve the quality of life of the patients. Current challenges in saliva collection are also addressed to improve the quality of saliva samples and produce robust biomarkers for future use in clinical applications.
Accumulation of cancer-associated fibroblasts (CAFs) in the tumor microenvironment is associated with poor prognosis and recurrence of colorectal cancer (CRC). Despite their prominent roles in colorectal carcinogenesis, there is a lack of robust and specific markers to classify the heterogeneous and highly complex CAF populations. This has resulted in confusing and misleading definitions of CAFs in cancer niche. Advancements in molecular biology approaches have open doors to reliable CAF marker detection methods in various solid tumors. These discoveries would contribute to more efficient screening, monitoring and targeted therapy of CRC thus potentially will reduce cancer morbidity and mortality rates. This review highlights current scenarios, dilemma, translational potentials of CAF biomarker and future therapeutic applications involving CAF marker identification in CRC.
A case of chronic mucocutaneous candidiasis in a Malaysian child who subsequently developed disseminated tuberculosis and toxoplasmosis is described. The phenotype of her peripheral blood mononuclear cells showed discordance for her T cell markers. The presence of a subpopulation of CD2-/CD3+ mononuclear cells leading to an immunodeficiency state is consistent with failure of activation of CD2-mediated alternative pathway resulting in immunodeficiency. Such abnormal CD2-/CD3+ subpopulations have been described in lepromatous leprosy and foetal abortuses.
Chronic pancreatitis is a difficult disease to treat. Worldwide, alcohol is the most common aetiology but based on recent studies it is clear that genetic susceptibility plays an important role in determining disease. Several important genetic mutations have been identified. The prevalence of chronic pancreatitis appears to be lower in Asia although very high rates have been reported in parts of India. Severe intractable pain is the predominant presenting complaint of patients. The natural history of the disease and the onset of exocrine and endocrine insufficiency depend on the classification of disease as early onset, late-onset or alcohol associated. Complications of chronic pancreatitis are important and include pseudocyst formation, bile duct and duodenal strictures.
Janus kinase (JAK) inhibitors, a novel class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), have shown their safety and efficacy in rheumatoid arthritis (RA) and are being intensively tested in other autoimmune and inflammatory disorders. Targeting several cytokines with a single small compound leads to blocking the physiological response of hundreds of genes, thereby providing the background to stabilize the immune response. Unfortunately, blocking many cytokines with a single drug may also bring some negative consequences. In this review, we focused on the activity of JAK inhibitors in the cardiovascular system of patients with RA. Special emphasis was put on the modification of heart performance, progression of atherosclerosis, lipid profile disturbance, and risk of thromboembolic complications. We also discussed potential pathophysiological mechanisms that may be responsible for such JAK inhibitor-associated side effects.
Identifying the nutrition problems of Asia and the Pacific is made difficult by the enormous geographic, socioeconomic and cultural diversity that exists in these areas. With increasing longevity and reduced infant mortality, the more chronic diseases are becoming increasingly important. For almost 90% of the countries that keep such data in the Western Pacific Region of WHO, at least three of the five leading causes of death are noncommunicable diseases. Nevertheless undernutrition is still the most important nutritional problem in the Region. Even though there have been some encouraging declines in the proportion of malnourished under 5-year-olds, increasing populations have meant the actual numbers have not declined. Vitamin A deficiency, iodine deficiency disorders and iron deficiency anaemia remain major public health problems in many countries. There is evidence that vitamin A deficiency is appearing in countries in which it has not previously been a problem. New challenges are occurring, such as childhood obesity, the susceptibility of undernourished populations to the human immunodeficiency virus and the increase in noncommunicable diseases. The three arms of clinical nutrition: therapeutic, research and public health will need to work closely to meet the considerable and continuing threat posed by the nutrition-related diseases.
Different probiotic strains are incorporated into cultured-milk drinks by respective manufacturers with the common aim of providing health benefits to the consumers. Four common cultured-milk products (brands N, S, V and Y) were evaluated for their quality of probiotic strains used, based on the susceptibility of the probiotics to various pH levels simulated to mimic the gastrointestinal system. Results showed that brands Y and V have higher initial probiotic inoculum compared to brands N and S although probiotics from brands N and S were more tolerant to pH 3. Generally, all probiotic strains preferred higher pH with highest viability of Lactobacillus spp., Bifidobacterium spp., and Streptococcus thermophilus observed at pH 8.1. Our study also discovered that among the four brands tested, brand V contained probiotic strains which are most likely to remain viable after passage through the gastrointestinal system.
Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. Much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis.