Impact of the COVID-19 pandemic on child malnutrition in Selangor, Malaysia: A pilot study.

BACKGROUND: Child malnutrition risk factors are globally recognized, but the specific impact of the COVID-19 pandemic on the prevalence of child malnutrition, considering socioeconomic burdens and changes in family lifestyles, remains underexplored. This study aims to identify the significance of COVID-19-related factors in relation to the prevalence of child malnutrition in Selangor, Malaysia. METHODS: Purposive sampling was employed in this pilot study to select the households with under-5 children and, a structured questionnaire was developed to gather data. Chi-squared tests, logistic regression modelling and World Health Organisation AnthroPlus software-based visualization were used for analyses. RESULTS: The present study's findings indicate that demographic and social factors, including 'Citizenship,' 'Type of House,' 'Number of Earning Members,' 'Father's Highest Educational Level,' and 'Number of Children in a Family,' have a statistically significant association with Wasting. Additionally, the mother's 'Highest Educational Level' is found to be linked to underweight prevalence. Within COVID-19 factors, "COVID-19 Impact on Employment/Business" demonstrated significance for both stunting and wasting. Multivariate analysis revealed disparities in childhood malnutrition by gender, age, and factors such as "COVID-19 impact on children's physical activity" and "COVID-19 impact on children's decrease in health over the last two weeks." CONCLUSIONS: This study identified COVID-19 factors alongside sociodemographic variables with statistically significant relationships impacting childhood malnutrition in Selangor, Malaysia. The results underscored the substantial influence of the COVID-19 pandemic on child malnutrition prevalence. Decision-makers at family and community levels can benefit by considering these factors in their actions. However, the study's limitation lay in its dataset, urging larger-scale analyses to explore further sub-categories of the examined variables.

Prevalence and Associated Factors Related to Tobacco Consumption Among University Students in Malaysia.

Tobacco consumption is one of the major public health concerns worldwide. Moreover, alternative tobacco and nicotine products (ATNPs) are growing in popularity, especially among young adults in the past decade. The study aimed to determine the prevalence and associated sociodemographic factors of tobacco consumption among university students. A cross-sectional study was carried out among 338 university students of a private Malaysian university from March to April 2021. Data was collected using a self-administered online questionnaire with items including sociodemographic information, user status of tobacco consumption and types of tobacco product used. Descriptive statistics, Pearson's chi-square test, Fisher's exact test and simple and multiple logistic regression analyses were performed using the IBM SPSS version 26.0 to analyse the data. The prevalence of tobacco consumption in this study was 8.6% and the main tobacco product used was manufactured cigarettes. In Pearson's chi square test and Fisher's exact test, current use of tobacco was significantly associated with nationality, ethnicity, religion, school, current level of education and parents, siblings and friends use of tobacco (p<0.05). In simple and multiple logistic regression analysis, being non-Malaysian, Indian, Muslim, year 4 student and having parents or siblings who used tobacco, all had statistically significant associations with the current use of tobacco (p<0.05). Findings of this study showed that the use of tobacco among university students is concerning and warrants the need to develop and implement a strategic anti-tobacco program to limit this behaviour among university students.

The impact of triple doses vaccination and other interventions for controlling the outbreak of COVID-19 cases and mortality in Australia: A modelling study.

COVID-19 is a significant public health problem around the globe, including in Australia. Despite this, Australia's Ministry of Health has expanded COVID-19 control measures widely, logistical trials exist, and the disease burden still needs more clarity. One of the best methods to comprehend the dynamics of disease transmission is by mathematical modeling of COVID-19, which also makes it possible to quantify factors in many places, including Australia. In order to understand the dynamics of COVID-19 in Australia, we examine a mathematical modeling framework for the virus in this study. Australian COVID-19 actual incidence data from January to December 2021 was used to calibrate the model. We also performed a sensitivity analysis of the model parameters and found that the COVID-19 transmission rate was the primary factor in determining the basic reproduction number (R0). Gradually influential intervention policies were established, with accurate effect and coverage regulated with the help of COVID-19 experts in Australia. We simulated data for the period from April 2022 to August 2023. To ascertain which of these outcomes is most effective in lowering the COVID-19 burden, we here assessed the COVID-19 burden (as shown by the number of incident cases and mortality) under a range of intervention scenarios. Regarding the policy of single intervention, the fastest and most efficient way to lower the incidence of COVID-19 is via increasing the first-dose immunization rate, while an improved treatment rate for the afflicted population is also helps to lower mortality in Australia. Furthermore, our results imply that integrating more therapies at the same time increases their efficacy, particularly for mortality, which significantly reduced with a moderate effort, while lowering the number of COVID-19 instances necessitates a major and ongoing commitment.

Knowledge, attitudes, and practices of female health care service providers on female genital mutilation in Somalia: A cross-sectional study.

BACKGROUND: Despite a strong international standpoint against female genital mutilation, the prevalence of female genital mutilation in Somalia is extremely high. OBJECTIVES: This study assessed the knowledge, attitude, and practice of female genital mutilation among female health care service providers in order to formulate appropriate policies and programs to eliminate this harmful practice. DESIGN: Facility-based cross-sectional survey conducted in 2019 among female doctors and nurses working in Banadir Hospital, Mogadishu, Somalia. METHODS: A total of 144 female health care service providers were randomly selected, and data were collected through a pre-tested, semi-structured questionnaire. Quantitative data were analyzed by using the statistical software SPSS (Version 21), and qualitative data were analyzed thematically in accordance with the objectives of the study. RESULTS: The study found that about three-fifths of the respondents had undergone some forms of female genital mutilation during their life. An overwhelming majority believed that female genital mutilation practices were medically harmful, and a majority of them expressed their opinion against the medicalization of the practice of female genital mutilation. The study also observed a significant association between participants' age and their negative attitudes regarding the legalization of female genital mutilation. CONCLUSION: Health care service providers' effort is critical to eliminating this harmful practice from the Somalian society. Strong policy commitment and a comprehensive health-promotion effort targeting the parents and community leaders are essential to avert the negative impact of female genital mutilation.

Effect of total population, population density and weighted population density on the spread of Covid-19 in Malaysia.

Since November 2019, most countries across the globe have suffered from the disastrous consequences of the Covid-19 pandemic which redefined every aspect of human life. Given the inevitable spread and transmission of the virus, it is critical to acknowledge the factors that catalyse transmission of the disease. This research investigates the relation of the external demographic parameters such as total population, population density and weighted population density on the spread of Covid-19 in Malaysia. Pearson correlation and simple linear regression were utilized to identify the relation between the population-related variables and the spread of Covid-19 in Malaysia using data from 15th March 2020 to 31st March 2021. As a result, a strong positive significant correlation between the total population and Covid-19 cases was found. However, a weak positive relationship was found between the density variable (population density and weighted population density) and the spread of Covid-19. Our findings suggest that the transmission of Covid-19 during lockdown (Movement Control Order, MCO) in Malaysia was more readily explained by the demographic variable population size, than population density or weighted population density. Thus, this study could be helpful in intervention planning and managing future virus outbreaks in Malaysia.

c-Src activation as a potential marker of chemical-induced skin irritation using tissue-engineered skin equivalents.

Skin irritancy to topically applied chemicals is a significant problem that affects millions of people worldwide. New or modified chemical entities must be tested for potential skin irritancy by industry as part of the safety and toxicity profiling process. Many of these tests have now moved to a non-animal-based format to reduce experiments on animals. However, these tests for irritancy potential often rely on monolayer cultures of keratinocytes that are not representative of the skin architecture or tissue-engineered human skin equivalents (HSE) using complex multi-gene expression panels that are often cumbersome and not amenable for high throughput. Here, we show that human skin equivalents increase abundance of several phosphorylated kinases (c-Src, c-Jun, p53, GSK3α/ß) in response to irritant chemical stimulation by phosphokinase array analysis. Specific phosphorylation of c-SrcY419 was confirmed by immunoblotting and was plasma membrane-associated in basal/spinous cells by phospho-specific immunohistochemistry. Moreover, c-SrcY419 phosphorylation in response to the irritants lactic acid and capsaicin was inhibited by the c-Src inhibitors KB-SRC and betaine trimethylglycine. These data provide the first evidence for c-Src specific activation in response to chemical irritants and point to the development of new modes of rapid testing by immunodetection for first-pass screening of potential irritants.

Footwear and insole design parameters to prevent occurrence and recurrence of neuropathic plantar forefoot ulcers in patients with diabetes: a series of N-of-1 trial study protocol.

BACKGROUND: Foot complications occur in conjunction with poorly controlled diabetes. Plantar forefoot ulceration contributes to partial amputation in unstable diabetics, and the risk increases with concomitant neuropathy. Reducing peak plantar forefoot pressure reduces ulcer occurrence and recurrence. Footwear and insoles are used to offload the neuropathic foot, but the success of offloading is dependent on patient adherence. This study aims to determine which design and modification features of footwear and insoles improve forefoot plantar pressure offloading and adherence in people with diabetes and neuropathy. METHODS: This study, involving a series of N-of-1 trials, included 21 participants who had a history of neuropathic plantar forefoot ulcers. Participants were recruited from two public hospitals and one private podiatry clinic in Sydney, New South Wales, Australia. This trial is non-randomised and unblinded. Participants will be recruited from three sites, including two high-risk foot services and a private podiatry clinic in Sydney, Australia. Mobilemat™ and F-Scan® plantar pressure mapping systems by TekScan® (Boston, USA) will be used to measure barefoot and in-shoe plantar pressures. Participants' self-reports will be used to quantify the wearing period over a certain period of between 2 and 4 weeks during the trial. Participant preference toward footwear, insole design and quality-of-life-related information will be collected and analysed. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the software NVivo (version 12) will be utilised for the qualitative data analysis. DISCUSSION: This is the first trial assessing footwear and insole interventions in people with diabetes by using a series of N-of-1 trials. Reporting self-declared wearing periods and participants' preferences on footwear style and aesthetics are the important approaches for this trial. Patient-centric device designs are the key to therapeutic outcomes, and this study is designed with that strategy in mind. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000699965p. Registered on June 23, 2020.

Effectiveness of High-Intensity Interval Training and Continuous Moderate-Intensity Training on Blood Pressure in Physically Inactive Pre-Hypertensive Young Adults.

The likelihood of pre-hypertensive young adults developing hypertension has been steadily increasing in recent years. Despite the fact that aerobic exercise training (AET) has demonstrated positive results in lowering high blood pressure, the efficacy of different types of AET among pre-hypertensive young adults has not been well-established. The objective of this study was to evaluate the effectiveness of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) on the blood pressure (BP) of physically inactive pre-hypertensive young adults. In total, 32 adults (age 20.0 ± 1.1 years and BMI 21.5 ± 1.8) were randomly assigned to three groups: HIIT, CMT and control (CON). The HIIT and CMT groups participated in 5 weeks of AET, while the CON group followed a DASH diet plan only. The HIIT protocol consisted of a 1:4 min work to rest ratio of participants, at an 80−85% heart rate reserve (HR-reserve) and a 40−60% HR-reserve, respectively, for 20 min; the CMT group exercised at 40−60% of their HR-reserve continuously for 20 min. In both the HIIT and CMT groups, systolic blood pressure (SBP) (3.8 ± 2.8 mmHg, p = 0.002 vs. 1.6 ± 1.5 mmHg, p = 0.011) was significantly reduced, while significant reductions in the diastolic blood pressure (DBP) (2.9 ± 2.2 mmHg, p = 0.002) and mean arterial pressure (MAP) (3.1 ± 1.6 mmHg, p < 0.0005) were noted only in the HIIT group. No significant differences in SBP (−0.4 ± 3.7 mmHg, p = 0.718), DBP (0.4 ± 3.4 mmHg, p = 0.714), or MAP (0.1 ± 2.5 mmHg, p = 0.892) were observed in the CON group. Both HIIT and CMT decreased BP in physically inactive pre-hypertensive young adults; however, HIIT yielded more beneficial results in terms of reducing the SPB, DBP and MAP.

Determining an effective short term COVID-19 prediction model in ASEAN countries.

The challenge of accurately short-term forecasting demand is due to model selection and the nature of data trends. In this study, the prediction model was determined based on data patterns (trend data without seasonality) and the accuracy of prediction measurement. The cumulative number of COVID-19 affected people in some ASEAN countries had been collected from the Worldometers database. Three models [Holt's method, Wright's modified Holt's method, and unreplicated linear functional relationship model (ULFR)] had been utilized to identify an efficient model for short-time prediction. Moreover, different smoothing parameters had been tested to find the best combination of the smoothing parameter. Nevertheless, using the day-to-day reported cumulative case data and 3-days and 7-days in advance forecasts of cumulative data. As there was no missing data, Holt's method and Wright's modified Holt's method showed the same result. The text-only result corresponds to the consequences of the models discussed here, where the smoothing parameters (SP) were roughly estimated as a function of forecasting the number of affected people due to COVID-19. Additionally, the different combinations of SP showed diverse, accurate prediction results depending on data volume. Only 1-day forecasting illustrated the most efficient prediction days (1 day, 3 days, 7 days), which was validated by the Nash-Sutcliffe efficiency (NSE) model. The study also validated that ULFR was an efficient forecasting model for the efficient model identifying. Moreover, as a substitute for the traditional R-squared, the study applied NSE and R-squared (ULFR) for model selection. Finally, the result depicted that the prediction ability of ULFR was superior to Holt's when it is compared to the actual data.

Analyzing the Impact of Demographic Variables on Spreading and Forecasting COVID-19.

The aim of this study is to analyse the coronavirus disease 2019 (COVID-19) outbreak in Bangladesh. This study investigates the impact of demographic variables on the spread of COVID-19 as well as tries to forecast the COVID-19 infected numbers. First of all, this study uses Fisher's Exact test to investigate the association between the infected groups of COVID-19 and demographical variables. Second, it exploits the ANOVA test to examine significant difference in the mean infected number of COVID-19 cases across the population density, literacy rate, and regions/divisions in Bangladesh. Third, this research predicts the number of infected cases in the epidemic peak region of Bangladesh for the year 2021. As a result, from the Fisher's Exact test, we find a very strong significant association between the population density groups and infected groups of COVID-19. And, from the ANOVA test, we observe a significant difference in the mean infected number of COVID-19 cases across the five different population density groups. Besides, the prediction model shows that the cumulative number of infected cases would be raised to around 500,000 in the most densely region of Bangladesh, Dhaka division.

Determination of Chemical Irritation Potential Using a Defined Gene Signature Set on Tissue-Engineered Human Skin Equivalents.

There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full-thickness human skin equivalent or human ex vivo skin and gene signatures determined for known irritants and nonirritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2, and matrix metalloproteinase gene MMP-3) that could distinguish potential irritants from nonirritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system.

Meta-analysis of single-cell RNA-seq data reveals phenotypic switching of immune cells in severe COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the global coronavirus disease 2019 (COVID-19) pandemic. Despite several single-cell RNA sequencing (RNA-seq) studies, conclusions cannot be reached owing to the small number of available samples and the differences in technology and tissue types used in the studies. To better understand the cellular landscape and disease severity in COVID-19, we performed a meta-analysis of publicly available single-cell RNA-seq data from peripheral blood and lung samples of COVID-19 patients with varying degrees of severity. Patients with severe disease showed increased numbers of M1 macrophages in lung tissue, while the number of M2 macrophages was depleted. Cellular profiling of the peripheral blood showed a marked increase of CD14+, CD16+ monocytes and a concomitant depletion of overall B cells and CD4+, CD8+ T cells in severe patients when compared with moderate patients. Our analysis indicates the presence of faulty innate-to-adaptive switching, marked by a prolonged innate immune response and a dysregulated adaptive immune response in severe COVID-19 patients. Furthermore, we identified cell types with a transcriptome signature that can be used as a prognostic biomarker for disease state prediction and the effective therapeutic management of COVID-19 patients.

SARS-CoV-2 infection initiates interleukin-17-enriched transcriptional response in different cells from multiple organs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a pandemic. Paucity of information concerning the virus and therapeutic interventions have made SARS-CoV-2 infection a genuine threat to global public health. Therefore, there is a growing need for understanding the molecular mechanism of SARS-CoV-2 infection at cellular level. To address this, we undertook a systems biology approach by analyzing publicly available RNA-seq datasets of SARS-CoV-2 infection of different cells and compared with other lung pathogenic infections. Our study identified several key genes and pathways uniquely associated with SARS-CoV-2 infection. Genes such as interleukin (IL)-6, CXCL8, CCL20, CXCL1 and CXCL3 were upregulated, which in particular regulate the cytokine storm and IL-17 signaling pathway. Of note, SARS-CoV-2 infection strongly activated IL-17 signaling pathway compared with other respiratory viruses. Additionally, this transcriptomic signature was also analyzed to predict potential drug repurposing and small molecule inhibitors. In conclusion, our comprehensive data analysis identifies key molecular pathways to reveal underlying pathological etiology and potential therapeutic targets in SARS-CoV-2 infection.

Mapping the role of pH-adjusted potassium in diabetic ketoacidosis: Hypokalemia and the patient outcomes.

BACKGROUND: Incidence of hypokalemia during the management of diabetic ketoacidosis (DKA) is high despite detailed potassium replacement guidelines in its treatment. AIM: We aimed to find the role of pH-adjusted potassium (pHK ) in the development of hypokalemia, and their mutual impact on patient outcomes during DKA management. METHODOLOGY: Adult DKA patient's admission data of preceding 3 years (2015-2017) were retrospectively clerked. Outcomes of interest were time to develop hypokalemia and to terminate emergency department (ED) care (hours), severity of hypokalemia and hospitalisation length (days). Linear regression was used to determine significant associations/predictors. RESULTS: The study was concluded on 85 patients. Hypokalemia was observed in nearly 3/4th of all admissions and occurred by the time of ED care termination. Each 1 mmol/L increase in pHK significantly (a) reduced the degree of hypokalemia by 0.07 mmol/L, (b) delayed time to develop hypokalemia by 4.58 hours, (c) and reduced the ED care time by 1.28 hours. Arterial pH was the other factor significantly delaying time to develop hypokalemia (36.25 hours) and facilitating early discharge from ED (13.86 hours). Moreover, each 1 mmol/L reduction in the degree of hypokalemia increased hospitalisation length by 1.86 days. Though significant, acute kidney injury negligibly increased hospitalisation length by 0.01 days. CONCLUSION: pH-adjusted potassium shall be used as a marker for hypokalemia and to initiate potassium replacement instead of measured serum potassium in DKA. Utilising pHK will help to avoid hypokalemia, reduce its severity and shorten ED care which will subsequently reduce hospitalisation length. We expect pHK to improve pharmacoeconomics in the future.

Identification of nucleoporin 93 (Nup93) that mediates antiviral innate immune responses.

RIG-I-like receptors (RLRs) are cytoplasmic sensors for viral RNA that elicit antiviral innate immune responses. RLR signaling culminates in the activation of the protein kinase TBK1, which mediates phosphorylation and nuclear translocation of IRF3 that regulates expression of type I interferon genes. Here, we found that Nucleoporin 93 (Nup93), components of nuclear pore complex (NPC), plays an important role in RLR-mediated antiviral responses. Nup93-deficient RAW264.7 macrophage cells exhibited decreased expression of Ifnb1 and Cxcl10 genes after treatment with a synthetic RLR agonist stimulation as well as Newcastle Disease Virus infection. Silencing Nup93 in murine primary macrophages and embryonic fibroblasts also resulted in reduced expression of these genes. IRF3 nuclear translocation during RLR signaling was impaired in Nup93-deficient RAW264.7 cells. Notably, the activation of TBK1 during RLR signaling was also decreased in Nup93-deficient cells. We found that Nup93 formed a complex with TBK1, and Nup93 overexpression enhanced TBK1-mediated IFNß promoter activation. Taken together, our findings suggest that Nup93 regulates antiviral innate immunity by enhancing TBK1 activity and IRF3 nuclear translocation.

Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch.

The incidence of sensitive skin with stinging and itch following chemical exposure in products such as cosmetics is increasing, but molecular mechanisms underlying this pathophysiology remain understudied. Here we performed transcriptional analysis of reconstructed human epidermis (RHE) 1, 6, and 24 h following topical lactic acid (LA) application, a known inducer of the sensitive skin reaction. Since little is known about the specific role of keratinocyte transcriptional changes in mediating stinging and itch, we performed pathway analysis using several publically available databases and then focused on significantly changed transcripts involved in stress responses and itch signaling using the Comparative Toxicogenomics Database. LA treatment induced damage-associated genes HSPA1A, DDIT3, IL1A, and HMGB2. Neurotrophic factors including BDNF, ARTN, PGE2, and chemokines were also upregulated. Stimulation of the RHE with 5% LA did not reduce cell viability, but reduced the trans-epidermal electric resistance, suggesting barrier dysfunction. Accordingly, skin barrier formation genes such as filaggrins (FLG, FLG2) and corneodesmosin (CDSN) were downregulated. To our knowledge, this is the first study focusing on transcriptional changes underlying the stinging response of keratinocytes upon LA stimulation. While follow-up research is needed, this study provides new insight into the mechanisms underlying the sensitive skin reaction.

Early events in hepatitis B virus infection: From the cell surface to the nucleus.

While most adults are able to clear acute hepatitis B virus (HBV) infection, chronic HBV infection is recalcitrant to current therapy because of the persistence of covalently closed circular DNA in the nucleus. Complete clearance of the virus in these patients is rare, and long-term therapy with interferon and/or nucleoside analogues may be required in an attempt to suppress viral replication and prevent progressive liver damage. The difficulty of establishing HBV infection in cell culture and experimental organisms has hindered efforts to elucidate details of the HBV life cycle, but it has also revealed the importance of the cellular microenvironment required for HBV binding and entry. Recent studies have demonstrated an essential role of sodium-taurocholate cotransporting polypeptide as a functional receptor in HBV infection, which has facilitated the development of novel infection systems and opened the way for more detailed understanding of the early steps of HBV infection as well as a potential new therapeutic target. However, many gaps remain in understanding of how HBV recognizes and attaches to hepatocytes prior to binding to sodium-taurocholate cotransporting polypeptide, as well as events that are triggered after binding, including entry into the cell, intracellular transport, and passage through the nuclear pore complex. This review summarizes current knowledge of the initial stages of HBV infection leading to the establishment of covalently closed circular DNA in the nucleus.

Abnormal development of placenta in HtrA1-deficient mice.

Abnormal levels of High temperature requirement A1 (HtrA1) protein have been repeatedly observed in sera and placentas of preeclampsia patients. To understand the functions of HtrA1 in placentation and in the etiology of preeclampsia, we established HtrA1(-/-) mice. HtrA1(-/-) mice show intrauterine growth retardation, and their placentas are small due to a reduced size of the junctional zone and aberrant vascularization in the labyrinth at the mid-gestation stage. HtrA1 is expressed by Tpbpa-positive trophoblast precursors in the outer ectoplacental cone and junctional zone from embryonic day 7.5 to 10.5. In the HtrA1(-/-) placenta, Tpbpa-positive cell precursors are decreased in the early stage. Spongiotrophoblasts and glycogen trophoblast cells, both of which differentiate from Tpbpa-positive precursors, are consequently decreased in the junctional zone. Fewer spiral artery-associated trophoblast giant cells, another cell type derived from Tpbpa-positive precursors, invade the decidua and associate with maternal arteries in the HtrA1(-/-) placenta than in the wild type placenta. Maternal arteries in the HtrA1(-/-) decidua have narrower lumens, thicker arterial walls, and more vascular smooth muscle cells remaining in the walls than those in the wild type decidua, indicating impaired remodeling of maternal arteries. These results indicate that HtrA1 plays important roles in the differentiation of trophoblasts from Tpbpa-positive precursors in the ectoplacental cone. Insufficient levels of HtrA1 cause poor placental development and intrauterine growth retardation, due to aberrant trophoblast differentiation and consequent defects in maternal artery remodeling, and may contribute to the onset of preeclampsia.

HtrA1 is induced by oxidative stress and enhances cell senescence through p38 MAPK pathway.

Genetic predisposition and senescence of retinal pigment epithelium induced by oxidative stress are major contributors to age-related macular degeneration (AMD). Single-nucleotide polymorphisms in HTRA1 are strongly linked to the onset of AMD. In this study, we examine the role of HtrA1 in premature senescence and cell death induced by oxidative stress. HtrA1 mRNA and protein were up-regulated during premature senescence induced by H2O2 in both mouse embryonic fibroblasts (MEFs) and ARPE-19 cells. Expression of the senescence markers p21(CIP1/WAF1) and p16(INK4a), and SA-ß-galactosidase activity, were higher in HtrA1+/- MEFs than in HtrA1-/- MEFs. HtrA1+/+ and HtrA1+/- MEFs were more resistant than HtrA1-/- MEFs to H2O2-induced cell death. Activation of p38 MAPK by oxidative stress was quicker in HtrA1+/- MEFs than in HtrA1-/- MEFs. The effects of excess HtrA1 were examined by transient transfection of cells with HtrA1 expression vectors or by addition of recombinant proteins. Excess wild type HtrA1 accelerated premature senescence of MEFs and ARPE-19 cells, while the protease-inactive HtrA1 S328A did not. HtrA1-induced senescence was abrogated by inhibition of p38 MAPK. We conclude that HtrA1 is induced by oxidative stress and promotes premature cell senescence through p38 MAPK in a protease activity-dependent manner.

A Cobb Douglas stochastic frontier model on measuring domestic bank efficiency in Malaysia.

Banking system plays an important role in the economic development of any country. Domestic banks, which are the main components of the banking system, have to be efficient; otherwise, they may create obstacle in the process of development in any economy. This study examines the technical efficiency of the Malaysian domestic banks listed in the Kuala Lumpur Stock Exchange (KLSE) market over the period 2005-2010. A parametric approach, Stochastic Frontier Approach (SFA), is used in this analysis. The findings show that Malaysian domestic banks have exhibited an average overall efficiency of 94 percent, implying that sample banks have wasted an average of 6 percent of their inputs. Among the banks, RHBCAP is found to be highly efficient with a score of 0.986 and PBBANK is noted to have the lowest efficiency with a score of 0.918. The results also show that the level of efficiency has increased during the period of study, and that the technical efficiency effect has fluctuated considerably over time.