Biomarkers for colorectal cancer chemotherapy: Recent updates and future perspective.

During the last few decades, the treatment options available for patients with metastatic colorectal cancer (mCRC) have undergone continuous improvements, transitioning from conventional chemotherapy to targeted therapy. These therapeutic innovations have led to significant improvements in patient clinical outcomes. However, there remains a need to improve the outcome for many CRC patients. Chemotherapy remains a cornerstone of CRC treatment, but the wide variability in tumour response and adverse reactions to chemotherapy poses a challenge to cancer treatment management. As a result, there is an unmet need to identify predictive biomarkers of chemotherapeutic response to guide treatment decisions. In this review, we summarise the conventional biomarkers used to predict chemotherapy responses in CRC and provide an overview of emerging predictive biomarkers based on the current understanding of the molecular biology of treatment response. Finally, we explore the challenges and future prospects of biomarker discovery to improve the prediction of patient response and ensure optimal treatment management for patients with metastatic CRC.

Effectiveness of Decision Aid in Men with Localized Prostate Cancer: a Multicenter Randomized Controlled Trial at Tertiary Referral Hospitals in an Asia Pacific Country.

There are several treatment options for localized prostate cancer with very similar outcome but vary in terms of technique and side effect profiles and risks. Considering the potential difficulty in choosing the best treatment, a patient decision aid (PDA) is used to help patients in their decision-making process. However, the use and applicability of PDA in a country in Asia Pacific region like Malaysia is still unknown. This study aims to evaluate the effectiveness of a PDA modified to the local context in improving patients' knowledge, decisional conflict, and preparation for decision making among men with localized prostate cancer. Sixty patients with localized prostate cancer were randomly assigned to control and intervention groups. A self-administered questionnaire, which evaluate the knowledge on prostate cancer (23 items), decisional conflict (10 items) and preparation for decision-making (10 items), was given to all participants at pre- and post-intervention. Data were analyzed using independent T test and paired T test. The intervention group showed significant improvement in knowledge (p = 0.02) and decisional conflict (p = 0.01) from baseline. However, when compared between the control and intervention groups, there were no significant differences at baseline and post-intervention on knowledge, decisional conflict and preparation for decision-making. A PDA on treatment options of localized prostate cancer modified to the local context in an Asia Pacific country improved patients' knowledge and decisional conflict but did not have significant impact on the preparation for decision-making. The study was also registered under the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12614000668606 registered on 25/06/2014.

Health literacy levels and its determinants among people with asthma in Malaysian primary healthcare settings: a cross-sectional study.

BACKGROUND: Limited health literacy among people with asthma is associated with poor adherence to self-management activities, thus poor clinical outcomes. This study aimed to determine the prevalence of health literacy level and its determinants among people with asthma in the Malaysian primary healthcare settings. METHOD: A cross-sectional study was conducted among participants aged > 18 years with asthma who attended five primary health clinics in Malaysia. Systematic random sampling was employed with a final sample of 550 participants. The questionnaires included the validated Malay version of Health Literacy Scale (HLS) and asthma control questionnaire (ACQ). Statistical analysis was done using SPSS version 25. Multiple logistic regression was performed to determine the determinants for limited health literacy. RESULTS: The participants mean age of the participants was 48 (SD15.4) years. Most of the participants were women (64%) and of Malay ethnicity (51.1%). Nearly half had a secondary level of education, n = 112, (45.8%). Mean duration of asthma diagnosis is 20.6 (SD 15.9) years. More than half (62.5%) had a family history of asthma. About half (50.9%) had uncontrolled asthma, with 87.3% self-rated themselves as having controlled asthma. About a third (29.1%) received education on of asthma action plan, but only 7.1% of these owned a written version an asthma action plan. Limited health literacy accounts for 60.5% of the participants. The significant determinants for limited health literacy included lower educational attainment (p < 0.001), family history of asthma (p = 0.034), < 20 years duration of asthma diagnosis (p = 0.031) and not receiving asthma action plan education (p < 0.001). CONCLUSION: In this study population, more than half of the people living with asthma were found to have limited health literacy, which was associated with not having received self-management education supported by an asthma action plan. Future interventions should include strategies that ensure they meet the needs of people with limited health literacy.

Validation of a KHV antibody enzyme-linked immunosorbent assay (ELISA).

Koi herpesvirus (KHV) causes KHV disease (KHVD). The virus is highly contagious in carp or koi and can induce a high mortality. Latency and, in some cases, a lack of signs presents a challenge for virus detection. Appropriate immunological detection methods for anti-KHV antibodies have not yet been fully validated for KHV. Therefore, it was developed and validated an enzyme-linked immunosorbent assay (ELISA) to detect KHV antibodies. The assay was optimized with respect to plates, buffers, antigens and assay conditions. It demonstrated high diagnostic and analytical sensitivity and specificity and was particularly useful at the pond or farm levels. Considering the scale of the carp and koi industry worldwide, this assay represents an important practical tool for the indirect detection of KHV, also in the absence of clinical signs.

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye.

Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL- 6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TO-related dry eye or other ocular surface inflammatory disorders.

Identification of immunogenic proteins of Candida parapsilosis by serological proteome analysis.

AIMS: Systemic candidiasis is the leading fungal bloodstream infection, and its incidence has been on the rise. Recently, Candida parapsilosis has emerged as an increasingly prevalent fungal pathogen, but little is known about its antigenic profile. Hence, the current work was performed to discover immunogenic proteins of C. parapsilosis using serological proteome analysis. METHODS AND RESULTS: Cell wall proteins extracted from C. parapsilosis were resolved by two-dimensional electrophoresis followed by immunoblotting using antisera from experimentally infected mice. Mass spectrometry analysis of the 32 immunoreactive protein spots resulted in the identification of 12 distinct proteins. Among them, 11 proteins were known antigens of Candida albicans, whereas Idh2p was identified for the first time as an immunogenic protein of Candida species. Recombinant Idh2p was expressed in Escherichia coli, and its antigenicity was verified by immunoblot analysis. CONCLUSIONS: An immunoproteomic approach was successfully applied to identify immunogenic proteins of C. parapsilosis, with Idh2p as a novel candidate antigen. The identified antigens may serve as potential biomarkers for development of diagnostic assay and/or vaccine for C. parapsilosis. SIGNIFICANCE AND IMPACT OF THE STUDY: This work represents the first immunoproteomic analysis of C. parapsilosis, which provides new insights into host-pathogen interactions and pathogenesis of C. parapsilosis. The immunogenic proteins could be studied as biomarker candidates for C. parapsilosis.

Immunoproteomic analysis of antibody response to cell wall-associated proteins of Candida tropicalis.

AIMS: This study was conducted to identify antigenic proteins of Candida tropicalis that are targeted by the host immune system. METHODS AND RESULTS: An immunoproteomic approach was used to discover antigens from cell wall of C. tropicalis that were recognized by sera from experimentally infected mice. This resulted in the identification of twelve distinct proteins, of which ten have been previously reported as antigens of Candida albicans. For the remaining two proteins, Idh2p has been described as an antigen of Candida parapsilosis, whereas Kgd2p is revealed for the first time as an antigenic protein for Candida species. These two antigens were expressed as recombinant proteins in Escherichia coli and were shown to be specifically recognized by sera from infected host on Western blot. CONCLUSIONS: The present work investigated immunoproteome of C. tropicalis and identified several biomarker candidate antigens, with Kgd2p as a novel immunogenic protein that could be associated with pathogenesis of C. tropicalis. SIGNIFICANCE AND IMPACT OF THE STUDY: Findings from this study help to improve current understanding on host response to C. tropicalis infection and provide new insights into immune-pathogenesis of C. tropicalis. Besides, the immunogenic proteins could be considered as targets for the development of immunodiagnostic assay and/or vaccine.

Ambient light intensity affecting ultrasound operator detection of liver lesions in cine-clips.

INTRODUCTION: Ambient light (AL) is an important factor to improve ultrasound pathology detection. However, there are no established room AL levels recommended during an ultrasound examination. We aim to examine the diagnostic accuracy using different intensity of AL for the detection of liver lesions in anonymised pre-recorded cine-clips. METHODS: Eight ultrasound operators with 5-14 years' professional experiences were prospectively recruited to evaluate 51 randomised cine-clips directly from one ultrasound machine. These 15-s clips of the right lobe of the liver in longitudinal and transverse planes were meant to simulate the ultrasound examination. Operators reviewed all cine-clips and responded to two questions per cine-clip regarding their detection performance under 3 AL settings; 3, 15 and 25 lux, at one lighting per visit. A repeat visit under each AL was performed to assess for intra-operator variability. Each operator completed six visits in total, with at least a 2-day washout period. The operators' performance was compared against imaging reference standards from contrast CT/MRI for cine-clips with lesion and serial US for those without. RESULTS: AL with highest degree of diagnostic accuracy was found to be at 25 lux. Results from 8 operators revealed sensitivity ranged from 79% to 100%, specificity ranged from 94% to 100%. Positive and negative predictive values were up to 100% with AL at 25 lux. Both intra-and interrater reliability were excellent at 0.85-1.0 (0.79-0.98) and 0.98 (0.97, 0.99) respectively, with AL at 25 lux. CONCLUSION: This study proved that ambient light intensity affects the ultrasound operator detection of liver lesions on cine-clips. IMPLICATIONS FOR PRACTICE: Identifying suitable AL levels will influence future ultrasound room construct.

The outcome of patients with renal involvement in pediatric-onset systemic lupus erythematosus--a 20-year experience in Asia.

Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age, but 15-20% of cases are diagnosed during childhood. It is important for physicians to understand the epidemiology and clinical presentation for early detection and diagnosis of this disease in difference races. The aim of this retrospective review was to provide a 20-year experience for initial clinical and laboratory manifestations and outcomes in pediatric-onset SLE (pSLE) in a medical center in Asia. We reviewed medical records between April 1990 and June 2012 of patients with a diagnosis of International Classification of Diseases, Ninth Revision (ICD-9) code 710.0 (SLE), who admitted or received follow-up in the Department of Pediatrics at Chang Chung Memorial Hospital. Patients with a diagnosis of SLE prior to their 18th birthday and followed up at our hospital were eligible for inclusion in this study. Medical records regarding age, gender, date of birth and diagnosis, clinical manifestations at diagnosis, laboratory results, image studies and the classification criteria were reviewed. Patients received regular outpatient department follow-up and laboratory survey every 1-6 months. The study cohort consisted of 189 patients; 164 females (86.87%) and 25 males (13.23%). The overall mean age at pSLE diagnosis was 12.62 ± 2.77 years. The most common clinical symptom was malar rash, followed by arthritis and oral ulcers. There was no significant difference in clinical and laboratory manifestations between females and males. More than half of the patients presented with renal involvement initially. The most common histological finding was Class IV lupus nephritis (LN), especially in males (p = 0.034) and young age. Even with severe LN, the rate of end-stage renal disease (ESRD) was low if adequate treatment was initiated. The 5, 10 and 15-year ESRD-free survival rates were 95.4%, 94.0% and 89.9% in patients with biopsy-proven LN. However, infection was the leading cause of mortality. Therefore, aggressive treatment for major organ involvement is important, but physicians must also be aware of fatal infection. The overall survival rates were 5 years: 93.4% and 10-20 years: 89.6%.

Type 2 Diabetes Mellitus Patient Profiles, Diseases Control and Complications at Four Public Health Facilities- A Cross-sectional Study based on the Adult Diabetes Control and Management (ADCM) Registry 2009.

INTRODUCTION: Diabetes care at different healthcare facilities varied from significantly better at one setting to no difference amongst them. We examined type 2 diabetes patient profiles, disease control and complication rates at four public health facilities in Malaysia. MATERIALS AND METHODS: This study analyzed data from diabetes registry database, the Adult Diabetes Control and Management (ADCM). The four public health facilities were hospital with specialist (HS), hospital without specialist (HNS), health clinics with family physicians (CS) and health clinic without doctor (CND). Independent risk factors were identified using multivariate regression analyses. RESULTS: The means age and duration of diabetes in years were significantly older and longer in HS (ANOVA, p< 0.0001). There were significantly more patients on insulin (31.2%), anti-hypertensives (80.1%), statins (68.1%) and antiplatelets (51.2%) in HS. Patients at HS had significantly lower means BMI, HbA1c, LDL-C and higher mean HDL-C. A significant larger proportion of type 2 diabetes patients at HS had diabetes-related complications (2-5 times). Compared to the HS, the CS was more likely to achieve HbA1c ≤ 6.5% (adjusted OR 1.2) and BP target < 130/80 mmHg (adjusted OR 1.4), the HNS was 3.4 times more likely not achieving LDL-C target < 2.6 mmol/L. CONCLUSION: Public hospitals with specialists in Malaysia were treating older male Chinese type 2 diabetes patients with more complications, and prescribed more medications. Patients attending these hospitals achieved better LDL-C target but poorer in attaining BP and lower HbA1c targets as compared to public health clinics with doctors and family physicians.

Diabetic retinopathy in native and non-native Sarawakians--findings from the Diabetic Eye Registry.

This study aims to determine the risk factors associated with diabetic retinopathy (DR) among natives and non-natives Sarawakians who were seen at 3 public hospitals and one health clinic in Sarawak. It is a cross sectional study where data on patients with DM were collected by staff at these healthcare facilities and entered into the web-based Diabetic Eye Registry. Univariate and multivariate analysis was used to determine the association factors for DR. DR was significantly less associated with natives (24.4%) compared to non-native Sarawakians (34.1%) (p < 0.001). The odds of getting DR was higher in patients whose duration of DM was more than 20 years (OR = 2.6), who have renal impairment (OR = 1.7) and non-natives (OR = 1.4).

Moisture retention of glycerin solutions with various concentrations: a comparative study.

Various methods of evaluating a humectant's moisture retention have unique mechanisms. Hence, for designing advanced or efficient ingredients of cosmetic products, a clear understanding of differences among methods is required. The aim of this study was to analyze the moisture-retention capacity of glycerin, a common ingredient in cosmetic products. Specifically, this study applied gravimetric analysis, transepidermal water loss (TEWL) analysis, and differential scanning calorimetry (DSC) to examine the evaporation of glycerin solutions of different concentrations. The results revealed that the moisture-retention capacity of glycerin increased with the glycerin concentration from 0 to 60 wt%, and glycerin at concentration of 60-70 wt% did not exhibit weight change during the evaporation process. When the glycerin concentration exceeded 70 wt%, moisture sorption occurred in the glycerin solution. Furthermore, the results revealed a deviation between the evaporation rates measured using gravimetric analysis and those measured using TEWL analysis. However, normalizing the results of these analyses yielded the relative evaporation rates to water, which were consistent between these two analyses. DSC thermograms further confirmed the consistent results and identified two hydrated water microstructures (nonfreezable water and free water) in the glycerin solutions, which explained why the measured evaporation rate decreased with the glycerin concentration. These findings can be applied to prove the moisture-retention capacity of a humectant in cosmetic products by different measuring methods.

Ethnic differences in glycaemic control and complications: the adult diabetes control and management (ADCM), Malaysia.

INTRODUCTION: Ethnicity is an important factor in diabetes care. The understanding of its effect in this country may help to improve diabetes care, glycaemic control and diabetic complication rates. This study was to determine the diabetes control profile in relation to complication rates between the three main ethnics group in Malaysia. METHODS: This nested cross-sectional study was part of the Audit of Diabetes Control and Management (ADCM), an ongoing cohort patient registry focused on diabetes control and management in the primary care setting in Malaysia. This registry registers all diabetes patients aged 18 years old and above. Demographic data, diabetes duration, treatment modalities, as well as various risk factors and diabetes complications are reported. Data was handled by statisticians using STATA version 9. RESULTS: A total of 20330 patients from 54 health centers were registered at the time of this report. The majority were type 2 diabetics (99.1%) of whom 56.6% were female. The mean age was 57.9 years (SD 11.58). Malay accounted for 56.3%, Chinese 19.5% and Indian 22.5%. There were 30.3% who attained HbA1c < 7%. Among three main races more Chinese had HbA1c < 6.5% (Chi-square: X2 = 71.64, p < 0.001), but did not show less complications of nephropathy (Indian suffered significantly more nephropathy, Chi-square: X2 = 168.76, p < 0.001), ischaemic heart disease (Chi-square: X2 = 5.67, p = 0.532) and stroke (Chi-square: X2 =15.38, p = 0.078). CONCLUSION: This study has again emphasized the existence of ethnic differences in glycaemic control and complication profiles. The Chinese diabetics suffer as many diabetes-related complications despite better glycaemic control. Further studies will need to look into other socio-genetic factors in order to provide a more personalized effective diabetes care.

High incidence of Plasmodium knowlesi malaria compared to other human malaria species in several hospitals in Malaysia.

Through the regional control programme, Malaysia has been successfully reducing the incidence of Plasmodium falciparum and Plasmodium vivax infections. However, the incidence of zoonotic malaria Plasmodium knowlesi infection is increasing and now has been the major cause of malaria in Malaysia especially Malaysian Borneo. The emergence of knowlesi infection has threatened the malaria elimination programme which the government aims to reduce the overall malaria infections by 2020. Unlike other benign human Plasmodium spp., P. knowlesi can cause fatal infections. The aim of this study was to determine the incidence and distribution of five human malaria parasites including P. knowlesi in Peninsular Malaysia and Malaysian Borneo. A total of 112 blood samples were collected from seven states and district hospitals in Peninsular Malaysia and Malaysian Borneo from year 2015 to 2016. The samples were examined by microscopy and further confirmed by nested PCR assay targeting 18S rRNA gene of Plasmodium spp. Following the nested PCR assays, a total of 54 (48.2%) samples were positive for P. knowlesi infections, 12 (10.7%) cases were positive for P. vivax infections, followed by 7 (6.3%) cases of P. falciparum and 4 (3.5%) cases of P. malariae. There were 3 cases (2.7%) of mixed infections (P. knowlesi/P. vivax). However, no cases were identified as P. ovale. A total of 32 (28.6%) cases were found as negative infections. LoopMediated Isothermal Amplification Assay (LAMP) was performed to confirm inconclusive results produced by microscopy and nested PCR. P. knowlesi showed the highest prevalence in Sarawak (n= 30), Sabah (n=13), Pulau Pinang (n=5) and Pahang (n=6). PCR and LAMP was not able to detect a large number of microscopy positive samples due to DNA degradation during storage and shipping. Among all the states involved in this study, the highest prevalence of P. knowlesi infection was found in Sabah and Sarawak.