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.

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.

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.

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.

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.

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.

Bodyweight status misperception among reproductive-aged women in primary care settings.

INTRODUCTION: It is common, and many international and local studies confirm this, that women of reproductive age misperceive their body-weight status. This phenomenon can lead to their being less likely to adopt a healthy lifestyle which later exposes them to increased health problems and risks including those of a gynecological and obstetric nature. Generally, there have been inconsistent findings concerning the association between the self-perceived weight status and sociodemographic factors, physical activities, and previous weight loss attempts of women of reproductive age in an Asian population like Malaysia. OBJECTIVE: This study aimed to determine the factors associated with body weight status misperception among reproductive-aged women at a primary care setting in Malaysia. METHODS: This is a cross-sectional study conducted at Klinik Kesihatan Durian Tunggal in 2016-2017. The questionnaire included questions on the perception of weight status, sociodemographic factors, smoking status, level of physical activity, and weight loss attempts. Logistic regressions were used for statistical analysis to examine the association between body weight status misperception and related factors. RESULTS: The study recruited 630 reproductive-aged women. The mean age and SD of the respondents was 32.7 + 8.9 years, and 84% of the respondents were Malays. More than three-quarters of the respondents (75.5%, n = 476) had received up to a secondary level of education. The majority of the respondents were in the overweight/obese group (59.4%, n = 374). The mean BMI of the respondents was 27.1 kg/m2 + 6.61. Approximately 65.4% (n = 412) of the respondents had an inactive lifestyle. However, 60% (n = 378) of the respondents reported that they had attempted to reduce their weight in the last year. A total of 141 respondents (22.4%) misperceived their weight status with 113 (80.1% ) of them underestimating their weight status. Women with primary-level education (OR: 3.545, 95% CI: 1.530-8.215, p = 0.003) and secondary-level education (OR: 1.933, 95% CI: 1.065-3.510, p = 0.030) had a greater likelihood of misperceiving their body weight status as compared to those who have a tertiary level of education. Women with no weight loss attempts were also at risk of body weight status misperception (OR: 1.850, 95% CI: 1.195, 2.865, p = 0.006). CONCLUSION: Bodyweight status misperception among reproductive-aged women was associated with a low level of education and with those who had made no weight loss attempts. Identifying women who are at risk of misperceiving their weight status would enable early counseling on weight management.

The implication of stigma on people living with HIV and the role of social support - A case report.

Despite the advancements made in the knowledge and treatment of the human immunodeficiency virus (HIV) since it was first discovered, people living with HIV (PLWH) continue to be stigmatized. This paper presents the case of an HIV-infected patient who delayed the necessary treatment due to stigma and ultimately presented with AIDS. Through social support, however, he was able to overcome his internalized stigma; he was finally willing to start on antiretroviral treatment (ART). This case report addresses the effect of stigma on and the role of social support in the management of an individual with HIV.

COVID-19: Four Paediatric Cases in Malaysia.

OBJECTIVE: This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. CASES: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. DISCUSSION: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.

Design, qualification & manufacture of ITER gravity supports.

As one of the key components to support all the magnet coils, the GS faces engineering challenge to its operational safety throughout the design, qualification and manufacturing process as a result of extreme loading condition. The structural safety of GS was confirmed by both the FEM analysis and the semi-prototype engineering test after a long time of design, qualification, manufacture and assembly. Welding the cooling pipe to the flexible plate without obvious deformation as well as tightening uniformly and precisely all the tie rods to clamp the plates were carried out successfully during manufacturing. The result of final vacuum leakage test indicates that the GS can not only meet the ITER vacuum requirement but also have no slow out-gassing. The first set of GS which has passed the ITER acceptance test is to be delivered to ITER construction site soon.

A role for G protein-coupled receptor 137b in bone remodeling in mouse and zebrafish.

G protein-coupled receptor 137b (GPR137b) is an orphan seven-pass transmembrane receptor of unknown function. In mouse, Gpr137b is highly expressed in osteoclasts in vivo and is upregulated during in vitro differentiation. To elucidate the role that GPR137b plays in osteoclasts, we tested the effect of GPR137b deficiency on osteoclast maturation and resorbing activity. We used CRISPR/Cas9 gene editing in mouse-derived ER-Hoxb8 immortalized myeloid progenitors to generate GPR137b-deficient osteoclast precursors. Decreasing Gpr137b in these precursors led to increased osteoclast differentiation and bone resorption activity. To explore the role of GPR137b during skeletal development, we generated zebrafish deficient for the ortholog gpr137ba. Gpr137ba-deficient zebrafish are viable and fertile and do not display overt morphological defects as adults. However, analysis of osteoclast function in gpr137ba-/- mutants demonstrated increased bone resorption. Micro-computed tomography evaluation of vertebral bone mass and morphology demonstrated that gpr137ba-deficiency altered the angle of the neural arch, a skeletal site with high osteoclast activity. Vital staining of gpr137ba-/- fish with calcein and alizarin red indicated that bone formation in the mutants is also increased, suggesting high bone turnover. These results identify GPR137b as a conserved negative regulator of osteoclast activity essential for normal resorption and patterning of the skeleton. Further, these data suggest that coordination of osteoclast and osteoblast activity is a conserved process among vertebrates and may have similar regulation.

Rapid detection of equine infectious anaemia virus nucleic acid by insulated isothermal RT-PCR assay to aid diagnosis under field conditions.

BACKGROUND: Control of equine infectious anaemia (EIA) currently depends on serological diagnosis of infected equids. However, recently infected equids may not produce detectable anti-EIAV antibodies up to 157 days post infection and so present a high transmission risk. Therefore, direct nucleic acid detection methods are urgently needed to improve EIAV surveillance and management programs in counties where the disease is endemic. OBJECTIVES: To evaluate a field-deployable, reverse transcription-insulated isothermal PCR (RT-iiPCR) assay targeting the conserved 5' untranslated region (5' UTR)/exon 1 of the tat gene of EIAV. STUDY DESIGN: The analytical and clinical performance of the newly developed EIAV RT-iiPCR was evaluated by comparison with a EIAV real-time RT-PCR (RT-qPCR) along with the AGID test. METHODS: Analytical sensitivity was determined using in vitro transcribed RNA containing the target area of the 5' UTR/tat gene and samples from two EIAV-positive horses. Specificity was verified using nine common equine viruses. Clinical performance was evaluated by comparison with EIAV RT-qPCR and AGID using samples derived from 196 inapparent EIAV carrier horses. RESULTS: EIAV RT-iiPCR did not react with other commonly encountered equine viruses and had equivalent sensitivity (95% detection limit of eight genome equivalents), with a concordance of 95.41% to conventional EIAV RT-qPCR. However, the RT-qPCR and RT-iiPCR had sensitivities of 43.75 and 50.00%, respectively, when compared to the AGID test. MAIN LIMITATIONS: Low viral loads commonly encountered in inapparent EIAV carriers may limit the diagnostic sensitivity of RT-PCR-based tests. CONCLUSIONS: Although EIAV RT-iiPCR is not sufficiently sensitive to replace the current AGID test, it can augment control efforts by identifying recently exposed or "serologically silent" equids, particularly as the latter often represent a significant transmission risk because of high viral loads. Furthermore, the relatively low cost and field-deployable design enable utilisation of EIAV RT-iiPCR even in remote regions.

Awareness of Colorectal Cancer among the Urban Population in the Klang Valley.

BACKGROUND: Colorectal cancer (CRC) is the second most common cancer in Malaysia. Awareness of risk factors, symptoms and warning signs of CRC will help in early detection. This paper presents the level of CRC awareness among the urban population in Malaysia. METHOD: A cross-sectional study was conducted from November 2015 till December 2016 at three government clinics in the Klang Valley. The validated Bowel Cancer Awareness Measure questionnaire in both English and Malay was used. The mean knowledge scores for the warning signs and risk factors of CRC in different socio-demographic groups were compared using ANOVA in SPSS version 23. Statistical significance was set at p<0.05 and a 95% confidence level. RESULTS: Of the 426 respondents, 29.1% were unable to recall the warning signs and symptoms of CRC. Average recall was less than two warning signs and symptoms (mean 1.62, SD 1.33). The mean total knowledge score for CRC was 9.91 (SD 4.78), with a mean knowledge scores for warning signs and risk factors at 5.27 (SD 2.74) and 4.64 (SD 2.78), respectively. Respondents with a higher level of education were found to have higher level of knowledge regarding the warning signs of CRC. There was a significant positive association between knowledge score for warning signs and level of confidence in detecting warning signs. Regarding the total knowledge score for CRC, 3.3% of respondents scored zero. For warning signs and risk factors, 8.2% and 8.5% of respondents had zero knowledge scores, respectively. CONCLUSIONS: Generally, awareness of CRC is poor among the urban population of Klang Valley. Greater education and more confidence in detecting warning signs are significantly associated with better knowledge of warning signs. CRC awareness programs should be increased to improve awareness.

A not to be missed cause in a child with atraumatic limp.

Children with musculoskeletal symptoms are commonly seen by general practitioners (GPs). Those that present with atraumatic limp pose a particular diagnostic challenge. Although uncommon, Perthes disease (PD) is an important cause of atraumatic limp in children and may result in debilitating consequences if missed. We put forward a case of delayed diagnosis of PD in a child, thus highlighting the need for a greater index of suspicion among GPs in approaching any child with a limp.