Intrinsic Capacity Impairment Patterns and their Associations with Unfavorable Medication Utilization: A Nationwide Population-Based Study of 37,993 Community-Dwelling Older Adults.

OBJECTIVES: Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study. DESIGN: A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020. SETTING AND PARTICIPANTS: The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach. METHODS: Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models. RESULTS: Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The "depression with cognitive impairment" group (EPP: aOR=4.35, 95% CI 3.52-5.39, p<0.01; PIMs: aOR=2.73, 95% CI 2.46-3.02, p<0.01) and the "impairment in all domains" group (EPP: aOR=9.02, 95% CI 7.16-11.37, p<0.01; PIMs: aOR=3.75, 95% CI 3.24-4.34, p<0.01) remained at higher odds for EPP and PIMs after adjustment. CONCLUSIONS: We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the "depression with cognitive impairment" and "impairment in all domains", was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility.

Post-acute Use of Opioids and Psychotropics in Patients after Hip Fracture: Unintended Consequences of Implementing Diagnosis-Related Grouping Payment.

OBJECTIVE: How implementing diagnostic-related grouping (DRG) payment affected the use of opioids and psychotropics by hip fracture patients following hospitalization remained unknown. DESIGN: A retrospective, pre-post design, cohort study of data excerpted from Taiwan's National Health Insurance Research database (NHIRD). SETTING AND PARTICIPANTS: Adults aged ≥ 65 years first admitted for hip fracture surgery from 2007 to 2012 were identified and divided into two 1:1 propensity-score matched groups: pre-DRG (2007-2009); DRG (2010-2012). MEASUREMENTS: The outcome measures were use of opioid and/or psychotropic drugs within 30 days, 90 days, 180 days, and 365 days after discharge. RESULTS: Data of 16,522 subjects were excerpted, and 8,261 propensity-score matched subjects each classified into the pre-DRG and DRG groups. After adjustment, the DRG group was significantly more likely than the pre-DRG group to have used antipsychotics after discharge from hip fracture surgery (≤30 days, ≤90 days, ≤180 days and ≤365 days). The DRG group also had significantly higher prescription rates of benzodiazepines and antipsychotics during the observation period. Moreover, the DRG group was less likely to use non-steroidal anti-inflammatory drugs (≤30 days, ≤90 days, ≤180 days and ≤365 days) and more likely to use acetaminophen (≤30 days, ≤180 days, and ≤365 days). CONCLUSIONS: In conclusion, DRG implementation in Taiwan substantially increased post-acute prescription of antipsychotic and psychotropic agents for hip fracture patients, and changed use of analgesics, which may result in suboptimal quality and safety for these patients. Further research is needed to evaluate the long-term outcomes of DRG implementation, and the potential benefits of appropriate post-acute care bundled with DRG payment.

The Adverse Effects of Physical Restraint Use among Older Adult Patients Admitted to the Internal Medicine Wards: A Hospital-Based Retrospective Cohort Study.

OBJECTIVES: To evaluate the negative effect of physical restraint use on the hospital outcomes of older patients. DESIGN: A retrospective cohort study. SETTING: Internal medicine wards of a tertiary medical center in Taiwan. PARTICIPANTS: Subjects aged 65 years and over who were admitted during April to Dec 2017 were recruited for study. MEASUREMENTS: Demographic data, geriatric assessments (polypharmacy, visual impairment, hearing impairment, activities of daily living before and after admission, risk of pressure sores, change in consciousness level, mood condition, history of falls in the previous year, risk of malnutrition and pain) and hospital conditions (admission route, department of admission, length of hospital stay and mortality) were collected for analysis. RESULTS: Overall, 4,352 participants (mean age 78.7±8.7 years, 60.2% = male) were enrolled and 8.3% had physical restraint. Results of multivariate logistic regression showed that subjects with physical restraints were at greater risk of functional decline (adjusted odds ratio 2.136, 95% confidence interval 1.322-3.451, p=0.002), longer hospital stays (adjusted odds ratio 5.360, 95% confidence interval 3.627-7.923, p<0.001) and mortality (adjusted odds ratio 4.472, 95% confidence interval 2.794-7.160, p<0.001) after adjustment for covariates. CONCLUSION: The use of physical restraints during hospitalization increased the risk of adverse hospital outcomes, such as functional decline, longer length of hospital stay and mortality.

Association between Orthostatic Hypotension and Frailty in Hospitalized Older Patients: a Geriatric Syndrome More Than a Cardiovascular Condition.

OBJECTIVES: To explore the association between orthostatic hypotension (OH) and frailty for hospitalized older patients and their vulnerable subgroups. DESIGN: A prospective, observational cross-sectional study. PARTICIPANTS: 693 older patients admitted to a geriatric evaluation and management unit. MEASUREMENTS: Barthel Index, Lawton's instrumental activities of daily living, clinical frailty scale, mini-mental state examination, geriatric depression scale, mini-nutritional assessment, and polypharmacy. RESULTS: Overall, the prevalence of OH and frailty was 26% and 36%, respectively. Subjects with OH were older, thinner, more commonly to have weakness, slowness, poorer physical function and higher levels of frailty. The prevalence of OH was substantially increased as higher levels of CFS (p for trend <0.001). Multivariate logistic regression showed significant association between OH and frailty (OR: 1.8, 95% CI: 1.2-2.7), but the association attenuated after adjustment for physical function. (OR: 1.4, 95% CI: 0.7-2.6). Nevertheless, associations between OH and frailty remained significant among vulnerable subgroups like women, subjects having weakness, slowness, poor cognitive function, polypharmacy or any IADL limitation. CONCLUSIONS: OH in hospitalized older patients was associated with frailty and multiple complex care needs, especially in the vulnerable subgroups. Further study is needed to clarify the roles of OH in clinical practice.

The lncRNA HOXA11-AS promotes glioma cell growth and metastasis by targeting miR-130a-5p/HMGB2.

OBJECTIVE: Long noncoding RNAs (lncRNAs) serve as important regulators of diverse types of cancer, including glioma. Nevertheless, their precise roles in cancers remain sufficiently unexplored. PATIENTS AND METHODS: Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to determine the levels of HOMEOBOX A11 antisense RNA (HOXA11-AS) and miR-130a-5p in glioma tissues and cell lines. Short hairpin RNAs (shRNAs) targeting HOXA11-AS or pcDNA3.1 were transfected into cells via a vector encoding HOXA11-AS to decrease or increase the level of HOXA11-AS. Cell Counting Kit-8 (CCK-8), colony formation, wound healing, flow cytometry and transwell assays were applied to assess the role of HOXA11-AS in glioblastoma cell growth, apoptosis and aggressiveness. The expression of N-cadherin and E-cadherin was determined using immunofluorescence staining. The expression of high-mobility group protein B2 (HMGB2) was determined using Western blot analysis in vitro and immunohistochemistry (IHC) staining in vivo. The direct target of HOXA11-AS and miR-130a-5p was confirmed using the Luciferase reporter assay. Glioblastoma cells were subcutaneously implanted into nude mice to determine the role of HOXA11-AS in tumor growth in vivo. RESULTS: In the current study, we demonstrated that the lncRNA HOXA11-AS was overexpressed in glioma. The overexpression of HOXA11-AS was correlated with advanced stages of glioma and poor prognosis. Downregulating HOXA11-AS expression significantly suppressed the proliferation, migration and invasion of glioma cells and increased their apoptosis. The growth of glioma cells in vitro was also suppressed by the downregulation of HOXA11-AS. Finally, we revealed that HOXA11-AS exerted its oncogenic effects by binding to miR-130a-5p, thereby neutralizing the suppressive effect of miR-130a-5p on HMGB2. CONCLUSIONS: Our results demonstrate that HOXA11-AS regulates the growth and metastasis of glioma by targeting the miR-130a-5p-HMGB2 signaling axis.

Association of New-Onset Diabetes Mellitus in Older People and Mortality in Taiwan: A 10-Year Nationwide Population-Based Study.

OBJECTIVE: Older patients with diabetes mellitus are at a higher risk of developing diabetic macro- and micro-vascular complications and cardiovascular diseases than younger diabetes mellitus patients. However, older diabetes mellitus patients are very heterogeneous in their clinical characteristics, diabetes mellitus-related complications and age at disease onset. This study aimed to evaluate the all-cause mortality rates and adverse health outcomes among older adults with new-onset diabetes mellitus through a nationwide population-based study. DESIGN: A retrospective cohort study. SETTING: 2001-2011 data of the National Health Insurance database. POPULATION: Nationally representative sample of Taiwanese adults aged 65 years and older with propensity score-matched controls. MAIN OUTCOME MEASURES: All-cause mortality and adverse health outcomes. RESULTS: During the study period, 45.3% of patients in the diabetes mellitus cohort and 38.8% in the non-diabetes mellitus cohort died. The adjusted relative risk for mortality in the diabetes mellitus cohort compared to the non-diabetes mellitus cohort was 1.23 (95% Confidence Interval [CI]=1.16-1.30) for males and 1.27 (95%CI=1.19-1.35) for females. During the follow-up period, 8.9% of the diabetes mellitus cohort and 5.8% of the non-diabetes mellitus cohort developed cardiovascular diseases; the diabetes mellitus cohort had an adjusted relative risk of cardiovascular complications compared to the non-diabetes mellitus cohort of 1.54 (95%CI=1.36-1.75) for men and 1.70 (95%CI=1.43-2.02) for women. The adjusted relative risk of mortality in the patients with hypoglycemia compared to non-hypoglycemia patients in the diabetes mellitus cohort was 2.33 (95%CI=1.81-3.01) for men and 2.73 (95%CI=2.10-3.52) for women after adjustment for age, Charlson comorbidity index, acute coronary syndrome, respiratory disease, cancer, infectious disease and nervous system disease at baseline. CONCLUSIONS: New-onset diabetes in older adults is associated with an increased risk of mortality, and hypoglycemia is an important marker of this association. Individualized care plans stratified by age at onset, duration of disease, comorbidity and functional status, as well as hypoglycemia avoidance, would benefit the management of diabetes in older adults.

Frailty Is a Geriatric Syndrome Characterized by Multiple Impairments: A Comprehensive Approach Is Needed.

OBJECTIVE: To evaluate the prevalence of frailty and the associated multimorbidity and functional impairments among community-dwelling middle-aged and elderly people in Taiwan. DESIGN: a cross-sectional study. SETTING: communities in I-Lan County of Taiwan. PARTICIPANTS: 1839 community-dwelling people aged 50 years and older. INTERVENTION: None. MEASUREMENTS: Frailty defined by Fried's criteria, Charlson's comorbidity index (CCI), Functional Autonomy Measurement System (SMAF), Center for Epidemiologic Studies Depression Scale (CES-D), Mini-Nutrition Assessment (MNA), Mini-Mental State Examination (MMSE), and Short Form-12 quality of life questionnaire. RESULTS: Overall, 1839 subjects (mean age: 63.9±9.3 years, 47.5% males) participated in this study and men were more likely to have higher educational level, more smoking and alcohol drinking habit. The prevalence of frailty was 6.8% in this study, while pre-frailty was 40.5% and 53.7% of all participants were robust. Compared to subjects with different frailty status, age, education year, alcohol drinking, hypertension, diabetes mellitus, hyperlipidemia, CCI, walking speed, handgrip strength, score of SMAF, CES-D, MNA, MMSE, quality of life were significantly different between groups (P all< 0.05). Older age, poorer physical function, poorer cognitive function, poorer nutritional status, more depressive symptoms, higher CCI and poorer quality of life were all independently associated with frailty. CONCLUSIONS: Frailty was not simply a geriatric syndrome, but the combination of multiple geriatric syndromes. Further study is needed to evaluate the clinical benefits of intervention programs for community-dwelling middle-aged and older people to reverse frailty and its associated functional impairments.

Fentanyl-induced cough is a risk factor for postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting (PONV) and fentanyl-induced cough (FIC) are two common anaesthesia-related events, which seem to have common risk factors. In this prospective cohort study, we investigate whether patients who have FIC during induction of anaesthesia have an increased incidence of PONV. METHODS: We studied adult non-smoking gynaecological surgical patients enrolled between July 1, 2011 and July 30, 2012. The presence of FIC during induction and the occurrence of PONV were recorded. Fentanyl-induced cough and other perioperative variables were subjected to multivariate analysis to determine the association between FIC and PONV. RESULTS: All 502 patients enrolled in this study had at least two risk factors for PONV, and 154 (31%) developed FIC. The incidence of PONV in the FIC group was higher than in the non-FIC group (56.5 vs 38.2%; P<0.0001). Multivariate logistic regression analysis found FIC to be a predictive risk factor for the development of PONV (adjusted odds ratio 2.08, 95% confidence interval 1.41-3.07). CONCLUSIONS: Non-smoking women undergoing gynaecological surgery who develop FIC during induction of anaesthesia have a higher incidence of PONV.

Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Société Française de Gériatrie et de Gérontologie) Workshop--Athens January 20-21, 2012.

UNLABELLED: Frailty tends to be considered as a major risk for adverse outcomes in older persons, but some important aspects remain matter of debate. OBJECTIVES: The purpose of this paper is to present expert's positions on the main aspects of the frailty syndrome in the older persons. PARTICIPANTS: Workshop organized by International Association of Gerontology and Geriatrics (IAGG), World Health Organization (WHO) and Société Française de Gériatrie et de Gérontologie (SFGG). RESULTS: Frailty is widely recognized as an important risk factor for adverse health outcomes in older persons. This can be of particular value in evaluating non-disabled older persons with chronic diseases but today no operational definition has been established. Nutritional status, mobility, activity, strength, endurance, cognition, and mood have been proposed as markers of frailty. Another approach calculates a multidimensional score ranging from "very fit" to "severely frail", but it is difficult to apply into the medical practice. Frailty appears to be secondary to multiple conditions using multiple pathways leading to a vulnerability to a stressor. Biological (inflammation, loss of hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors (isolation, financial situation) are involved in the vulnerability process. In clinical practice, detection of frailty is of major interest in oncology because of the high prevalence of cancer in older persons and the bad tolerance of the drug therapies. Presence of frailty should also be taken into account in the definition of the cardiovascular risks in the older population. The experts of the workshop have listed the points reached an agreement and those must to be a priority for improving understanding and use of frailty syndrome in practice. CONCLUSION: Frailty in older adults is a syndrome corresponding to a vulnerability to a stressor. Diagnostic tools have been developed but none can integrate at the same time the large spectrum of factors and the simplicity asked by the clinical practice. An agreement with an international common definition is necessary to develop screening and to reduce the morbidity in older persons.

Survival benefits of metabolic syndrome among older men aged 75 years and over in Taiwan.

BACKGROUND: Metabolic syndrome (MetS) was common in the elderly, but its prognostic significance in older old population remained unclear. The main purpose of this study was to evaluate the survival impact of MetS among older men aged 75 and over in Taiwan. METHODS: From 2008, residents aged 75 years and older of Banciao Veterans Home were invited for study and were followed for 3 years. All participants received history taking, physical examinations, and laboratory tests. Mortality was determined by Veteran Affairs Death Registry, which was linked to the National Death Registry. RESULTS: Overall, 680 men (mean age: 82.5±4.7 years) were enrolled for study and the prevalence of MetS was 31.6%. During the follow-up period, 140 (20.6%) participants died, and the causes of death included infectious diseases (62, 9.1%), cardiovascular disease (37, 5.4%), cancer (20, 2.9%), and others (21, 3.1%). MetS subjects had a significantly higher prevalence of hypertension, diabetes mellitus, and having higher body mass index, waist circumferences, systolic blood pressure, fasting blood glucose, serum triglyceride and lower HDL-C level than non-MetS subjects. However, MetS subjects were less likely to die during study period (16.3% vs. 22.6%, P=0.059). Multivariate logistic regression showed that older age (OR:1.04, 95% C.I.: 1.00-1.08, P=0.04), diabetes mellitus (OR: 2.10, 95% CI: 1.34-3.30, P=0.001) were independent risk factors for mortality; and serum total cholesterol and triglyceride were protective factors (OR: 0.99, 95% CI: 0.99-1.00, P=0.037 for cholesterol; OR: 0.99, 95% CI: 0.99-1.00, P=0.013 for triglyceride). Adjusted for age, diabetes mellitus, serum levels of total cholesterol, and triglyceride, MetS played a potential trend of survival benefits among study subjects (HR: 0.71, 95% CI: 0.45-1.12, P=0.144). CONCLUSIONS: The prevalence of MetS among men aged 75 years and over was 31.6%, and the 3-year mortality rate was 20.6%. Older age, diabetes mellitus, lower serum cholesterol and lower serum triglyceride were independent risk factors for mortality. Further investigation is needed to clarify the prognostic impact of MetS in older adults.

The health benefits of smoking cessation for adult smokers and for pregnant women in Taiwan.

OBJECTIVE: To assess the benefits of smoking cessation regarding mortality reduction after smokers quit, and regarding the health of newborns after smoking mothers quit. METHODS: Relative mortality risks (RR) for smokers aged 35 or older who quit years ago were calculated from the follow up of 71 361 civil servants and teachers recruited since 1989. Data from the Pregnancy Risk Assessment Monitoring System in Taipei City were used to calculate the odds ratios of body weights of newborns born to mothers of different smoking status. RESULTS: Mortality risk for ex-smokers was significantly lower than that of current smokers for all causes (18%), all cancer (22%), lung cancer (39%), and ischaemic heart disease (54%). These benefits were not distinguishable initially, up to five years, but by year 17 and thereafter, substantial benefits of cessation accrued. Two thirds of smoking women quit during the first trimester of pregnancy, and only 2.2% of mothers smoked throughout pregnancy. The newborns from smoking mothers were smaller than those from never smoking mothers, but, if these mothers quit early in the first trimester, birth weights were normal. CONCLUSIONS: The health benefits of smoking cessation, rarely reported for Asian populations, have been largely ignored by smokers in Taiwan, where cessation activities have been extremely limited. Findings of this study that risks from smoking can be attenuated or reversed should be widely communicated to motivate smokers to quit. Smokers should quit early, including smoking mothers, and not wait till medical conditions surfaced, to have the maximal benefits of cessation.

Hepatitis C virus infection-related Type 1 diabetes mellitus.

BACKGROUND: Hepatitis C virus (HCV) has been associated with Type 2 diabetes mellitus, and many other viral infections have been associated with Type 1 diabetes mellitus (Type 1 DM). An association between HCV and Type 1 DM, however, has never been reported. We report the case of a 66-year-old man who developed Type 1 DM 1 year after a blood transfusion-related HCV infection. Testing of serum specimens obtained in the weeks following blood transfusion demonstrated evidence of both acute HCV infection and development of Type 1 DM-related autoantibodies. CASE REPORT: A 66-year-old Taiwanese male received blood transfusions during coronary artery bypass surgery in 1987. Serum specimens, obtained as part of a study on post-transfusion hepatitis, demonstrated that the patient had no evidence of hepatitis C prior to transfusion, but developed acute HCV infection after transfusion. One year later, the patient, who had no personal or family history of diabetes, presented with diabetic ketoacidosis, and tests for C-peptide confirmed that he had Type 1 DM. Testing of pre- and post-operative serum specimens demonstrated that the patient developed positive tests for islet cell and glutamic acid decarboxylase antibodies 4 weeks after transfusion, concurrent with the development of acute HCV infection. CONCLUSIONS: The simultaneous development of HCV infection and diabetes-related autoantibodies suggest a relationship between HCV and Type 1 DM.

Prenatal three-dimensional ultrasound and magnetic resonance imaging evaluation of a fetal oral tumor in preparation for the ex-utero intrapartum treatment (EXIT) procedure.

Recent attempts at predelivery management of obstructed fetal airways have focused on the EXIT (ex-utero intrapartum treatment) procedure, which allows sufficient time to secure the fetal airway through preservation of uteroplacental gas exchange. We report a fetus with an exophytic oral tumor noted at 34 weeks of gestation. In this case, three-dimensional (3D) ultrasound allowed a complete and interactive evaluation of the tumor and related facial anatomy, and confirmed that access to the fetal airway was unlikely during delivery. Fetal magnetic resonance imaging (MRI) further demonstrated that the tumor originated in the nasopharynx and obstructed the upper airway. Both imaging results led to a final decision to offer an EXIT procedure for the neonate. At 36 weeks' gestation, a successful EXIT procedure was performed to reduce the risk of respiratory distress immediately after birth. This report highlights the value of 3D ultrasound and MRI as essential prerequisites for optimization of the triage process in selecting EXIT candidates.

Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation.

Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-kappaB), and salicylates have been shown to inhibit NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IkappaBalpha-DeltaN, a dominant-negative mutant that antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-kappaB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IkappaBalpha-DeltaN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-kappaB pathway.

The effect of human bcl-2 and bcl-X genes on dengue virus-induced apoptosis in cultured cells.

Infection of dengue viruses (DENs) can cause human dengue fever, hemorrhagic fever, or shock syndrome. Although DEN-induced apoptosis has been implicated in pathogenesis of the DEN-related diseases, the underlying mechanism remains largely unexplored. In this study, we investigated the effect of ectopic expression of human bcl-2 and bcl-X genes on DEN-induced apoptosis in cultured cells. We employed a human isolate of DEN serotype 2 (DEN-2), PL046, which not only caused cell-cycle arrest in the G1 phase but also induced apoptosis in infected baby hamster kidney (BHK-21) cells, murine neuroblastoma N18 cells, and human neuronal NT-2 cells. Our results reveal that overexpression of bcl-2 in fibroblast-like BHK-21 cells, although not inhibiting virus yields, delayed the process of DEN-induced apoptosis, thereby permitting surviving cells to become persistently infected. In contrast, stable bcl-2 expression in neuronal N18 cells failed to block DEN-induced apoptosis. On the other hand, Bcl-X(L), expressed predominantly in the nervous system, appeared to delay DEN's killing effect in neuronal N18 cells but not in fibroblast-like BHK-21 cells. In addition, inducible expression bcl-X(s), despite its proapoptotic property in other reported system, was found to merely accelerate cell death in DEN-infected N18 but not in infected BHK-21 cells. Thus, through studying the effect of human bcl-2-related genes, our results suggest that DEN infection may trigger target cells to undergo morphologically similar but biochemically distinct apoptotic pathways in a cell-specific manner.

Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80: analysis by cDNA microarray.

The ability of cells to rejoin DNA double-strand breaks (DSBs) usually correlates with their radiosensitivity. This correlation has been demonstrated in radiosensitive cells, including the Chinese hamster ovary mutant XRS-5. XRS-5 is defective in a DNA end-binding protein, Ku80, which is a component of a DNA-dependent protein kinase complex used for joining strand breaks. However, Ku80-deficient cells are known to be retarded in cell proliferation and growth as well as other yet to be identified defects. Using custom-made 600-gene cDNA microarray filters, we found differential gene expressions between the wild-type and XRS-5 cells. Defective Ku80 apparently affects the expression of several repair genes, including topoisomerase-I and -IIA, ERCC5, MLH1, and ATM. In contrast, other DNA repair-associated genes, such as GADD45A, EGR1 MDM2 and p53, were not affected. In addition, for large numbers of growth-associated genes, such as cyclins and clks, the growth factors and cytokines were also affected. Down-regulated expression was also found in several categories of seemingly unrelated genes, including apoptosis, angiogenesis, kinase and signaling, phosphatase, stress protein, proto-oncogenes and tumor suppressors, transcription and translation factors. A RT-PCR analysis confirmed that the XRS-5 cells used were defective in Ku80 expression. The diversified groups of genes being affected could mean that Ku80, a multi-functional DNA-binding protein, not only affects DNA repair, but is also involved in transcription regulation. Our data, taken together, indicate that there are specific genes being modulated in Ku80- deficient cells, and that some of the DNA repair pathways and other biological functions are apparently linked, suggesting that a defect in one gene could have global effects on many other processes.

Colorectal cancer in patients 20 years old or less in Taiwan.

BACKGROUND: Colorectal cancer (CRC) is predominantly a disease of the elderly population, but it sometimes occurs in young patients. The diagnosis of CRC in youngsters is often overlooked by physicians or presentation may be delayed. METHODS: With assistance from the cancer registry center of Taipei Veterans General Hospital, we collected data on all types of colorectal malignancy, including carcinoma, adenocarcinoma, or lymphoma in patients aged 20 or younger. All available medical charts and pathologic specimens were reviewed in detail. RESULTS: A total of 28 cases were analyzed. The leading presenting symptom was abdominal pain (92%). The locations of the primary tumors were evenly distributed, and the major histologic type was predominantly adenocarcinoma. However, the proportion of mucinous adenocarcinoma was higher than that in the older population. Most of the cases were advanced (11 tumors were classified as Dukes stage C and another 11 as Dukes stage D). The overall 5-year survival rate was 21%. CONCLUSIONS: Despite the rarity of CRC during the first two decades of life, physicians need to be aware of the possibility and to evaluate suggestive signs and symptoms by colonoscopy or barium enema. Family history of CRC, inflammatory bowel disease, previous polyps, or familial polyposis did not play a crucial role in this group of young patients.

Analysis of the steps involved in Dengue virus entry into host cells.

The initial steps of dengue viral entry have been divided into adsorption and penetration using acid glycine treatment to inactivate extracellular virus after attachment to baby hamster kidney (BHK) cells but prior to penetration. First, we showed that virus infection was accomplished within 2 h after adsorption. Second, the assay was used to examine the properties of dengue envelope E protein-specific monoclonal antibodies (MAbs), lectins, and heparin. We found that three MAbs, 17-2, 46-9, and 51-3, may neutralize dengue 2 virus (DEN-2) through inhibition of not only viral attachment but also of penetration. However, one MAb, 56-3.1, interfered specifically with attachment. Therefore, the functional domains of E protein involved in attachment and penetration may be different. Moreover, studies with lectins indicated that carbohydrates, especially alpha-mannose residues, present on the virion glycoproteins may contribute to binding and penetration of the virus into BHK and mosquito C6/36 cells. Finally, virus infectivity was inhibited by heparin through its blocking effects at both virus attachment and penetration. This suggests that cell surface heparan sulfate functions in both viral attachment and penetration of DEN-2 virus. In conclusion, our results further elucidated some aspects of the dengue virus entry process.