Clinicopathological study of gastric cancer in a Malaysian tertiary public health care centre.

INTRODUCTION: Gastric cancer (GC) is one of the leading causes of all new cancer cases globally. Although it is no longer reported in the top 10th most common cancer in Malaysia, geographical distribution and ethnic influences still obviously exist. MATERIALS AND METHODS: This is a retrospective analysis of histopathological records in a public tertiary health care centre in Malaysia. The computerised laboratory information system from the histopathology department of the hospital was retrieved for the period of 2005-2018. Descriptive analysis was done using Microsoft Excel. RESULTS: There was a total of 233 histologically confirmed GC cases. The burden of GC was observed to be an increasing trend from 2016 onwards. Among them, 64% were male and 36% were female. The youngest age of diagnosis was 19, while the oldest one was 93. Malaysian Chinese were found to have the highest incidences (41.63%), followed by Malays (32.19%) and Malaysian Indians (23.61%). All cases were of adenocarcinoma cell types and were found to have poorly differentiated in majority at the time of diagnosis. CONCLUSION: Although this report only represents one tertiary health care centre in Malaysia, the Indian Enigma was still observed, as stated in other literatures. Over time, the incidence of GC in Malays has increased. Consideration of lifestyle modifications, health education and Helicobacter pylori eradication in various nations' National Health Insurance plans, are encouraged as prevention is always better than treatment or cure, including the cost load.

Stillbirth rate in singleton pregnancies: a 20-year retrospective study from a public obstetric unit in Hong Kong.

INTRODUCTION: Although the stillbirth rate is low in Hong Kong, up to 50% of stillbirths have unclassifiable causes and up to one third of stillbirths have unexplained causes. This retrospective study investigated the underlying causes of singleton stillbirths in Hong Kong. METHODS: This study examined the prevalences and causes of stillbirths in a university tertiary obstetric unit between 2000 and 2019. Medical records were reviewed for all singleton pregnancies complicated by stillbirths. Causes of stillbirth were determined via clinical assessments and laboratory findings, then compared between 2000-09 and 2010-19. RESULTS: Overall perinatal mortality significantly decreased by 16.7%, from 5.52/1000 in 2000-09 to 4.59/1000 in 2010-19; the singleton stillbirth rate slightly decreased (from 3.27/1000 to 2.91/1000). These changes were related to early prenatal diagnostic improvements concerning congenital malformations and genetic disorders. Pre-eclampsia prevalence among singleton pregnancies increased from 1.5% to 1.7% because of increasing maternal age; the stillbirth rate among patients with pre-eclampsia decreased from 2.5% to 1.4%. Foetal growth restriction of unknown cause contributed to 16% of all stillbirths; this prevalence did not change over time. Moreover, foetal growth restriction was not diagnosed during routine antenatal care in 43.5% of patients. Thirty-six percent of all stillbirths were unexplained. The prevalences of stillbirth associated with chorioamnionitis and placental abruption did not change over time. CONCLUSIONS: Causes of stillbirth in Hong Kong have changed in the past 20 years because of altered demographic characteristics and improved prenatal testing. Further improvements should focus on early foetal growth restriction detection and preeclampsia prevention.

Perinatal mortality rate in multiple pregnancies: a 20-year retrospective study from a tertiary obstetric unit in Hong Kong.

INTRODUCTION: Multiple pregnancies have become more common, but their perinatal mortality rate remains higher than the rate among singleton pregnancies. This retrospective study investigated the prevalence and causes of perinatal mortality among multiple pregnancies in Hong Kong. METHODS: All multiple pregnancies in a university tertiary obstetric unit between 2000 and 2019 were reviewed, and the medical records of cases complicated by stillbirth and neonatal death were identified. The causes of perinatal mortality were determined based on clinical assessment and laboratory results, then compared between the first (2000-2009) and second (2010-2019) decades. RESULTS: The prevalence of multiple pregnancies increased from 1.41% in the first decade to 1.91% in the second decade (P<0.001). Compared with the first decade, the second decade had a lower stillbirth rate (14.72 vs 7.68 [both per 1000 births]; P=0.026), late neonatal death rate (4.78 vs 1.16 [both per 1000 livebirths]; P=0.030), and total mortality rate (25.32 vs 13.82 [both per 1000 births]; P=0.006). The decline in stillbirth rate was related to improvements in antenatal care and treatment. The decline in the late neonatal death rate was related to a reduction in preterm birth before 34 weeks (18.5% vs 15.2%; P=0.006), as well as an improvement in the mortality rate in the subgroup of 31-33 weeks (19.23 vs 0 [both per 1000 livebirths]; P=0.035). CONCLUSION: Although the prevalence of multiple pregnancies increased during the study period, the corresponding total perinatal mortality rate improved by 45.4%.

Neonatal mortality in singleton pregnancies: a 20-year retrospective study from a tertiary perinatal unit in Hong Kong.

INTRODUCTION: The global neonatal death (NND) rate has been declining in recent decades, but there are no comprehensive data concerning the characteristics of NNDs in Hong Kong. This study investigated the trends and aetiologies of NNDs among singleton pregnancies in Hong Kong. METHODS: This study included all cases of NND from singleton pregnancies in a tertiary hospital in Hong Kong between 2000 and 2019. The rates, clinical characteristics, and aetiologies of NND were compared between the first (2000-2009) and the second (2010-2019) decades. RESULTS: The NND rate decreased from 1.66/1000 livebirths (97 cases) in the first decade to 1.32/1000 livebirths (87 cases) in the second decade. Congenital or genetic abnormalities (82 cases) caused 44.6% of all NNDs. There was a significant reduction from 0.82/1000 livebirths in the first decade to 0.52/1000 livebirths in the second decade (P=0.037). Other causes of NND were prematurity (69 cases; 37.5%), sepsis (16 cases; 8.7%), hypoxic-ischaemic encephalopathy (15 cases; 8.2%), and sudden infant death syndrome (2 cases; 1.1%). Gestational age-specific neonatal mortality for moderately preterm neonates (31-33 weeks of gestation) significantly decreased from 34.73/1000 in 2000-2009 to 8.63/1000 in 2010-2019 (P=0.001), but there were no significant changes in neonatal mortality for other gestations. CONCLUSION: The NND rate in Hong Kong is among the lowest worldwide. Neonatal deaths in our centre declined over the past two decades, mainly because of improvements in the prenatal diagnosis and treatment of congenital or genetic abnormalities, as well as an improved survival rate among moderately preterm neonates.

Mammalian lectin arrays for screening host-microbe interactions.

Many members of the C-type lectin family of glycan-binding receptors have been ascribed roles in the recognition of microorganisms and serve as key receptors in the innate immune response to pathogens. Other mammalian receptors have become targets through which pathogens enter target cells. These receptor roles have often been documented with binding studies involving individual pairs of receptors and microorganisms. To provide a systematic overview of interactions between microbes and the large complement of C-type lectins, here we developed a lectin array and suitable protocols for labeling of microbes that could be used to probe this array. The array contains C-type lectins from cow, chosen as a model organism of agricultural interest for which the relevant pathogen-receptor interactions have not been previously investigated in detail. Screening with yeast cells and various strains of both Gram-positive and -negative bacteria revealed distinct binding patterns, which in some cases could be explained by binding to lipopolysaccharides or capsular polysaccharides, but in other cases they suggested the presence of novel glycan targets on many of the microorganisms. These results are consistent with interactions previously ascribed to the receptors, but they also highlight binding to additional sugar targets that have not previously been recognized. Our findings indicate that mammalian lectin arrays represent unique discovery tools for identifying both novel ligands and new receptor functions.

Readability and suitability of oral health education pamphlets produced by the Ministry of Health Malaysia.

INTRODUCTION: Printed health education materials can only be effective if they are readable and suitable for the target audience. This study examined the readability and suitability of oral health education (OHE) pamphlets produced by the Oral Health Program (OHP), Ministry of Health (MOH) Malaysia. METHODS: The Khadijah Rohani's Readability Formula (KRRF) and Suitability Assessment of Materials (SAM) instrument were used to assess the readability and suitability of the pamphlets respectively. All 23 Bahasa Malaysia pamphlets retrieved from the official portal of OHP on the 31st January 2019 were assessed for suitability. However, only five pamphlets were found to be eligible for readability assessment because the KRRF, the single formula available for Bahasa Malaysia text is applicable only for materials with 300 words or more. The readability is interpreted based on the level of formal education in Malaysia. RESULTS: All pamphlets achieved superior suitability rating with a minimum and maximum score of 75% and 95% respectively. However, a few pamphlets did not fulfil SAM superior and adequate criteria for the following factors and were rated not suitable: did not include summary (73.9%), have few or no headers (4.3%), did not use captions to explain graphics (17.4%), and did not provide interactive learning (21.7%). Readability of the pamphlets eligible for assessment ranged from primary six to secondary three. CONCLUSIONS: OHE pamphlets produced by the MOH are readable by most Malaysians. Most pamphlets are generally suitable for the intended audience although a few performed poorly in several areas.

Complementary and alternative medicine (CAM) information and support needs of Chinese-speaking cancer patients.

PURPOSE: Complementary and alternative medicine (CAM) is popular among Chinese-speaking cancer patients (CSCPs), but little research examines CAM use by Canadian CSCPs. The use of CAM is controversial because of potential interactions with conventional cancer treatments. The purpose of this study was to explore CSCPs' use of CAM, sources of CAM information, and decision support needs, as well as their experience of making CAM decisions. METHODS: A sequential, multi-method research design was used: a secondary data analysis of a CAM use survey conducted in a Western Canadian regional cancer agency followed by a qualitative interpretive description approach to inquiry using semi-structured interviews with CSPCs and support persons. RESULTS: More than 65% of CSCPs reported using CAM. CSCPs favored biologically-based therapies, including traditional Chinese medicine herbs and other natural health products. Many CSCPs were using CAM without adequate culturally appropriate information and decision support. Those who made decisions spontaneously relied on peers for advice whereas deliberate decision makers sought information from multiple sources, including peers and the Internet, selecting therapies congruent with their cultural health perspectives and previous experiences with CAM. CSCPs rarely spoke with oncology healthcare providers (HCPs) about CAM use. CONCLUSIONS: CSCPs reported using CAM at rates significantly higher than for non-CSCPs. Given the predominance of biological-based therapies and the lack of consultation with oncology HCPs, it is imperative that CAM use be assessed and documented to ensure CSCPs' safety during cancer treatment. Culturally appropriate information and decision support is required to ensure that CSCPs are making safe and informed CAM decisions.

Loss of adenylyl cyclase I activity disrupts patterning of mouse somatosensory cortex.

The somatosensory (SI) cortex of mice displays a patterned, nonuniform distribution of neurons in layer IV called the 'barrelfield' (ref. 1). Thalamocortical afferents (TCAs) that terminate in layer IV are segregated such that each barrel, a readily visible cylindrical array of neurons surrounding a cell-sparse center, represents a distinct receptive field. TCA arbors are confined to the barrel hollow and synapse on barrel-wall neurons whose dendrites are oriented toward the center of the barrel. Mice homozygous for the barrelless (brl) mutation, which occurred spontaneously in ICR stock at Université de Lausanne (Switzerland), fail to develop this patterned distribution of neurons, but still display normal topological organization of the SI cortex. Despite the absence of barrels and the overlapping zones of TCA arborization, the size of individual whisker representations, as judged by 2-deoxyglucose uptake, is similar to that of wild-type mice. We identified adenylyl cyclase type I (Adcy1) as the gene disrupted in brl mutant mice by fine mapping of proximal chromosome 11, enzyme assay, mutation analysis and examination of mice homozygous for a targeted disruption of Adcy1. These results provide the first evidence for involvement of cAMP signalling pathways in pattern formation of the brain.

Reward System in Late-Life Depression: a Cross-Sectional Case-Control Study.

OBJECTIVE: Anhedonia, commonly defined as a reduced ability to feel pleasure, is a core clinical symptom of late-life depression (LLD). Deficits in reward processing are hypothesised to be associated with anhedonia. We examined differences in reward sensitivity between patients with LLD and healthy controls and explored the associations between LLD-related symptomatology, global cognition, and the reward system. METHODS: The reward responsiveness of 63 patients with LLD and 58 healthy controls aged ≥60 years was assessed using the probabilistic reward learning task with an asymmetric reward schedule. RESULTS: Compared with healthy controls, patients with LLD displayed lower response bias and reward learning. Global cognition of all participants was positively correlated with response bias. In patients with LLD, anhedonia severity explained impaired reward learning. CONCLUSION: A deficit in reward processing is implicated in patients with LLD. Our findings suggest that executive dysfunction and anhedonia contribute to lower sensitivity to reward learning in patients with LLD.

Bat coronavirus was detected positive from insectivorous bats in Krau Wildlife Reserve Forest.

Bats are flying mammals with unique immune systems that allow them to hold many pathogens. Hence, they are recognised as the reservoir of many zoonotic pathogens. In this study, we performed molecular detection to detect coronaviruses, paramyxoviruses, pteropine orthoreoviruses and dengue viruses from samples collected from insectivorous bats in Krau Reserve Forest. One faecal sample from Rhinolophus spp. was detected positive for coronavirus. Based on BLASTN, phylogenetic analysis and pairwise alignment-based sequence identity calculation, the detected bat coronavirus is most likely to be a bat betacoronavirus lineage slightly different from coronavirus from China, Philippines, Thailand and Luxembourg. In summary, continuous surveillance of bat virome should be encouraged, as Krau Reserve Forest reported a wide spectrum of biodiversity of insectivorous and fruit bats. Moreover, the usage of primers for the broad detection of viruses should be reconsidered because geographical variations might possibly affect the sensitivity of primers in a molecular approach.

First detection of Babesia sp. in Bornean sun bear (Helarctos malayanus euryspilus Horsfield) in Sabah, Malaysia.

The Bornean sun bear, a subspecies of the endangered Malayan sun bear, resides only on Borneo Island and little is known about diseases or parasites that may impact their health. In 2019, blood and ticks were collected from 46 captive bears held at the Bornean Sun Bear Conservation Centre in Sabah, Malaysia during annual health examinations in response to previous blood smear analysis that revealed presumptive haemoparasites in more than half the resident bears. Polymerase chain reaction detected a unique Babesia sp. in one of the bears. Disease surveillance of mosquitoes trapped along the outer perimeter of the bears' outdoor enclosure did not reveal any malaria parasites. This research marks the first documented case in Bornean sun bears of both a Babesia sp. and the Ixodes tick Haemaphysalis nr koningsbergeri. More research on incriminating the vector and the effects of Babesia infection on the health of Bornean sun bears is needed. Due to the zoonotic nature of babesiosis, mitigative actions should be taken to protect any humans that work with or come into close contact with these captive bears or their enclosures.

A possible case of hantavirus infection in a Borneo orangutan and its conservation implication.

BACKGROUND: Natural infection of hantavirus in orangutans has never been reported. METHODS: Enzyme-linked immunosorbent assays (ELISA), Indirect immunofluorescence assay (IFA), and RT-PCR were used to diagnosis a suspected case in a pet orangutan in southern Taiwan. RESULTS: Although the RT-PCR result was negative, the high IgG titer in the beginning and its dramatic drop after treatments suggested a recent Seoul-type hantavirus infection. CONCLUSIONS: Hantavirus transmission and its potential damage to wild orangutans should not be overlooked.

Mapping frailty concepts to SNOMED CT.

BACKGROUND: Frailty is considered an emerging syndrome characterized by a decrease in physiological ability to respond to stressors, leading to increased morbidity and mortality rates. Frailty is distinguished from normal age-associated decline because it is a sharp and often rapid decline rather than a gradual slowing down of general functioning. The comprehensive geriatric assessment is currently considered the gold standard for identifying frailty in older adults. The electronic version of this tool is called the eCGA and is commonly included in electronic medical records (EMR) in primary care settings. OBJECTIVES: We explored the adequacy of SNOMED CT to represent frailty concepts by addressing three research questions: 1) What are the defining characteristics of frailty most commonly used in frailty assessment tools? 2) Are these characteristics captured within one or many frailty assessment tools? 3) Which data elements from existing tool(s) can be reliably mapped to existing SNOMED CT terms? METHODS: We conducted a literature search to explore the defining characteristics of frailty and the most commonly used assessment tools. We compared these findings to the components of frailty captured within the eCGA. We then used a descriptive study design to manually map concepts from the eCGA to SNOMED CT. RESULTS: Our literature review demonstrated that the eCGA contains all common defining characteristics of frailty. Unique assessment questions from the eCGA (n = 133) were manually mapped to SNOMED CT, using expert consensus. Of these, 72 % were direct matches, 17 % were one-to-many matches, and the remaining 11 % were non-matches. Two rounds of expert clinician mapping occurred; inter-rater reliability between the two clinicians was 0.75 (kappa). CONCLUSIONS/IMPLICATIONS: The resulting list of mapped eCGA elements to SNOMED CT terms can inform revisions to existing chronic disease databases to include frailty monitoring and surveillance.

Can Linked Electronic Medical Record and Administrative Data Help Us Identify Those Living with Frailty?

INTRODUCTION: Frailty is a complex condition that affects many aspects of patients' wellbeing and health outcomes. OBJECTIVES: We used available Electronic Medical Record (EMR) and administrative data to determine definitions of frailty. We also examined whether there were differences in demographics or health conditions among those identified as frail in either the EMR or administrative data. METHODS: EMR and administrative data were linked in British Columbia (BC) and Manitoba (MB) to identify those aged 65 years and older who were frail. The EMR data were obtained from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) and the administrative data (e.g. billing, hospitalizations) was obtained from Population Data BC and the Manitoba Population Research Data Repository. Sociodemographic characteristics, risk factors, prescribed medications, use and costs of healthcare are described for those identified as frail. RESULTS: Sociodemographic and utilization differences were found among those identified as frail from the EMR compared to those in the administrative data. Among those who were >65 years, who had a record in both EMR and administrative data, 5%-8% (n=191 of 3,553, BC; n=2,396 of 29,382, MB) were identified as frail. There was a higher likelihood of being frail with increasing age and being a woman. In BC and MB, those identified as frail in both data sources have approximately twice the number of contacts with primary care (n=20 vs. n=10) and more days in hospital (n=7.2 vs. n=1.9 in BC; n=9.8 vs. n=2.8 in MB) compared to those who are not frail; 27% (BC) and 14% (MB) of those identified as frail in 2014 died in 2015. CONCLUSIONS: Identifying frailty using EMR data is particularly challenging because many functional deficits are not routinely recorded in structured data fields. Our results suggest frailty can be captured along a continuum using both EMR and administrative data.

Development of comparable algorithms to measure primary care indicators using administrative health data across three Canadian provinces.

INTRODUCTION: Performance measurement has been recognized as key to transforming primary care (PC). Yet, performance reporting in PC lags behind even though high-performing PC is foundational to an effective and efficient health care system. OBJECTIVES: We used administrative data from three Canadian provinces, British Columbia, Ontario and Nova Scotia, to: 1) identify and develop a core set of PC performance indicators using administrative data and 2) examine their ability to capture PC performance. METHODS: Administrative data used included Physician Billings, Discharge Abstract Database, the National Ambulatory Care and Reporting System database, Census and Vital Statistics. Indicators were compiled based on a literature review of PC indicators previously developed with administrative data available in Canada (n=158). We engaged in iterative discussions to assess data conformity, completeness, and plausibility of results in all jurisdictions. Challenges to creating comparable algorithms were examined through content analysis and research team discussions, which included clinicians, analysts, and health services researchers familiar with PC. RESULTS: Our final list included 21 PC performance indicators pertaining to 1) technical care (n=4), 2) continuity of care (n=6), and 3) health services utilization (n=11). Establishing comparable algorithms across provinces was possible though time intensive. A major challenge was inconsistent data elements. Ease of data access, and a deep understanding of the data and practice context, was essential for selecting the most appropriate data elements. CONCLUSIONS: This project is unique in creating algorithms to measure PC performance across provinces. It was essential to balance internal validity of the indicators within a province and external validity across provinces. The intuitive desire of having the exact same coding across provinces was infeasible due to lack of standardized PC data. Rather, a context-tailored definition was developed for each jurisdiction. This work serves as an example for developing comparable PC performance indicators across different provincial/territorial jurisdictions.

Stimulation of neurite outgrowth in PC12 cells by EGF and KCl depolarization: a Ca(2+)-independent phenomenon.

MAP kinase activity is necessary for growth factor induction of neurite outgrowth in PC12 cells. Although NGF and EGF both stimulate MAP kinase activity, EGF does not stimulate neurite extension. We report that EGF, in combination with KCl, stimulates neurite outgrowth in PC12 cells. This phenomenon was independent of intracellular Ca2+ increases and not due to enhancement of MAP kinase activity over that seen with EGF alone. However, EGF plus KCl increased intracellular cAMP, and other cAMP elevating agents acted synergistically with EGF to promote neurite outgrowth. Stimulation of neurite outgrowth by cAMP and EGF was blocked by inhibitors of transcription suggesting that synergistic regulation of transcription by the cAMP and MAP kinase pathways may stimulate neurite growth.

Development of an optical biosensor for the detection of Trypanosoma evansi and Plasmodium berghei.

A laboratory prototype system that correlates murine blood absorbance with degree of infection for Plasmodium berghei and Trypanosoma avensi has been designed, constructed and tested. A population (n = 6) of control uninfected, Plasmodium infected and Trypanosoma infected BALB/c mice were developed and spectral absorption measurements pre and post infection were made every 3 days. A fibre optic spectrometer set-up was used as the basis of a laboratory prototype biosensor that uses the Beer Lambert Law to relate Ultraviolet-Visible-Near-infrared absorbance data to changes in murine blood chemistry post infection. Spectral absorption results indicate a statistically relevant correlation at a 650 nm with infection for Plasmodium from between 4 and 7 sampling days' post infection, in spite of significant standard deviations among the sample populations for control and infected mice. No significant spectral absorption change for Trypanosoma infection was been detected from the current data. Corresponding stained slides of control and infected blood at each sampling date were taken with related infected cell counts determined and these correlate well for Plasmodium absorbance at 650 nm.

Achieving cross provincial comparisons of osteoporosis screening performance from administrative health data.

Administrative databases can be used to measure healthcare performance. This can lead to identification of high-performing practice characteristics and inform innovations. However, a key challenge is that administrative data cannot be easily combined across provinces. Comparable measures must be defined across provinces but operationalized within each province. The purpose of this work is to provide an example of defining a population health concept, osteoporosis screening, and creating measures to examine it across British Columbia, Ontario, and Nova Scotia, Canada. TRANSFORMATION is a study that seeks to improve the science and reporting of Primary Health Care performance. We used administrative data from the above three provinces to examine osteoporosis screening in those aged 65 years and older. Challenges of databases with different data elements and levels of methods development (e.g. macros) can be overcome for purposes of cross-provincial comparisons. Flexibility of analytic methods and frequent communication is needed.

Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation.

Although Ca2+-stimulated cAMP response element binding protein- (CREB-) dependent transcription has been implicated in growth, differentiation, and neuroplasticity, mechanisms for Ca2+-activated transcription have not been defined. Here, we report that extracellular signal-related protein kinase (ERK) signaling is obligatory for Ca2+-stimulated transcription in PC12 cells and hippocampal neurons. The sequential activation of ERK and Rsk2 by Ca2+ leads to the phosphorylation and transactivation of CREB. Interestingly, the Ca2+-induced nuclear translocation of ERK and Rsk2 to the nucleus requires protein kinase A (PKA) activation. This may explain why PKA activity is required for Ca2+-stimulated CREB-dependent transcription. Furthermore, the full expression of the late phase of long-term potentiation (L-LTP) and L-LTP-associated CRE-mediated transcription requires ERK activation, suggesting that the activation of CREB by ERK plays a critical role in the formation of long lasting neuronal plasticity.

Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice.

Cyclic nucleotide-gated ion channels in olfactory sensory neurons (OSNs) are hypothesized to play a critical role in olfaction. However, it has not been demonstrated that the cAMP signaling is required for olfactory-based behavioral responses, and the contributions of specific adenylyl cyclases to olfaction have not been defined. Here, we report the presence of adenylyl cyclases 2, 3, and 4 in olfactory cilia. To evaluate the role of AC3 in olfactory responses, we disrupted the gene for AC3 in mice. Interestingly, electroolfactogram (EOG) responses stimulated by either cAMP- or inositol 1,4,5-triphosphate- (IP3-) inducing odorants were completely ablated in AC3 mutants, despite the presence of AC2 and AC4 in olfactory cilia. Furthermore, AC3 mutants failed several olfaction-based behavioral tests, indicating that AC3 and cAMP signaling are critical for olfactory-dependent behavior.