Subject(s)
Lymph Node Excision , Lymphedema , Melanoma , Humans , Melanoma/surgery , Melanoma/pathology , Lymphedema/etiology , Lymphedema/surgery , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Prospective Studies , Prognosis , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Leg/surgery , Inguinal Canal/surgery , Inguinal Canal/pathology , Postoperative Complications/etiology , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. METHODS: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex®) > 10 or change of L-Dex® > 10 from baseline. RESULTS: Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9-62.0%], 54.1% I-IL [CI 38.0-70.1%]) and lowest at 18 months (18.8% IL [CI 5.2-32.3%], 41.4% I-IL [CI 23.5-59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6-18.7%) and L-Dex® was 12.6 (IQR 9.0-17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. CONCLUSIONS: Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study's small sample did not have the statistical evidence to support an overall difference between the surgical groups.
Subject(s)
Inguinal Canal , Lymph Node Excision , Lymphedema , Melanoma , Skin Neoplasms , Humans , Melanoma/surgery , Melanoma/pathology , Lymphedema/etiology , Lymph Node Excision/adverse effects , Female , Male , Prospective Studies , Middle Aged , Follow-Up Studies , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Inguinal Canal/surgery , Inguinal Canal/pathology , Prognosis , Survival Rate , Leg , Aged , Adult , Postoperative Complications/etiology , Neoplasm StagingSubject(s)
Lymph Node Excision , Lymphedema , Melanoma , Humans , Lymphedema/etiology , Lymphedema/surgery , Melanoma/surgery , Melanoma/pathology , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Inguinal Canal/surgery , Inguinal Canal/pathology , Prognosis , Postoperative Complications/etiologyABSTRACT
BACKGROUND: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. OBJECTIVE: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. DESIGN: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. SETTING: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. MEASUREMENTS: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. RESULTS: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). CONCLUSIONS: The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.
Subject(s)
Aging/physiology , Cognitive Dysfunction , Predictive Value of Tests , Risk Assessment , Surveys and Questionnaires , Aged , Cardiometabolic Risk Factors , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cohort Studies , Female , Hearing Loss , Humans , Longitudinal Studies , Male , Middle Aged , Pilot Projects , Prevalence , Reproducibility of Results , Singapore/epidemiologyABSTRACT
This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in µ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.
Subject(s)
Bone Resorption , Osteoclasts , Animals , Cell Differentiation , Female , Lactobacillus , Mice , NF-kappa BABSTRACT
BACKGROUND: Studies suggest that nutritional interventions using the whole diet approach such as the Mediterranean diet may delay cognitive decline and dementia onset. However, substantial numbers of older adults are non-adherent to any ideally healthy dietary pattern and are at risk of malnutrition. OBJECTIVE: The present study investigated the relationship between global malnutrition risk and onsets of cognitive decline and neurocognitive disorders (NCD), including mild cognitive impairment (MCI) or dementia in community-dwelling older adults. METHODS: Participants aged ≥ 55 years in the Singapore Longitudinal Ageing Studies (SLAS) were assessed at baseline using the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA) and followed up 3-5 years subsequently on cognitive decline (MMSE drop ≥ 2) among 3128 dementia-free individuals, and incident neurocognitive disorders (NCD) among 2640 cognitive normal individuals. RESULTS: Individuals at high nutritional risk score (≥ 3) were more likely to develop cognitive decline (OR=1.42, 95%CI=1.01-1.99) and incident MCI-or-dementia (OR=1.64, 95%CI=1.03-2.59), controlling for age, sex, ethnicity, low education, APOE-e4, hearing loss, physical, social, and mental activities, depressive symptoms, smoking, alcohol, central obesity, hypertension, diabetes, low HDL, high triglyceride, cardiac disease, and stroke. Among ENIGMA component indicators, low albumin at baseline was associated with cognitive decline and incident NCD, and 5 or more drugs used, few fruits/vegetables/milk products daily, and low total cholesterol were associated with incident NCD. CONCLUSION: The ENIGMA measure of global malnutrition risk predicts cognitive decline and incident neurocognitive disorders, suggesting the feasibility of identifying vulnerable subpopulations of older adults for correction of malnutrition risk to prevent neurocognitive disorders.
Subject(s)
Cognitive Dysfunction , Neurocognitive Disorders , Nutritional Status , Aged , Aging , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Humans , Middle Aged , Neurocognitive Disorders/epidemiology , Neurocognitive Disorders/etiology , Singapore/epidemiologyABSTRACT
OBJECTIVES: China is facing an escalating demand of healthcare services from the middle-aged and elderly. Compared with the traditional view of health on symptoms and diseases, this study aimed to assess the heterogeneous health profiles of middle-aged and elderly Chinese by a person-centered approach. Furthermore, this study examined the effects of health profiles and associated factors on healthcare utilization within the context of China's multiple health insurance schemes. STUDY DESIGN: The study used the 2015 data of China Health and Retirement Longitudinal Study, a nationwide population-based sample of people aged 45 years and older. METHODS: Latent class analysis (LCA) was adopted to identify the heterogeneous health profiles. Two-part models were adopted to assess the effects of associated factors on healthcare utilization. RESULTS: Among 15,250 Chinese aged 45 years and older, six heterogeneous health profiles were identified and labeled as 'Quite Healthy', 'Relatively Healthy', 'Comprehensive Comorbidities', 'Functional Impairment', 'Severe Disability', and 'Relatively Frail'. The Relatively Frail profile was the heaviest healthcare user. The Severe Disability profile took the least use of outpatient services but had relatively high utilization of inpatient services and outpatient expenditure. The Comprehensive Comorbidities profile tended to have the smallest effect on the frequency of visits for both inpatient and outpatient services, but its effect on outpatient expenditure was high. After controlling for health profiles, the significant effects of different health insurance programs on healthcare utilization were discussed. CONCLUSIONS: Introducing health profiles by the person-centered approach of LCA has provided a holistic understanding of complex healthcare demands for middle-aged and elderly Chinese. It is valuable for policy makers to improve healthcare resource allocation targeted for the middle-aged and elderly.
Subject(s)
Health Status , Insurance, Health/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Aged , China , Female , Humans , Longitudinal Studies , Male , Middle AgedABSTRACT
INTRODUCTION: Type III endoleaks are a rare but potentially life-threatening complication post endovascular aortic aneurysm repair (EVAR). CASE REPORT: A 91-year-old Chinese female, presented to our accident and emergency department for severe back and abdominal pain. She had previously undergone an EVAR procedure twenty years ago for a 6.5 cm diameter infra-renal abdominal aortic aneurysm. A CT aortogram revealed a type III endoleak, with the contralateral limb found to be disconnected from the main graft body. She was successfully treated by relining the graft using an endovascular technique. DISCUSSION: The case highlights the need for life-long stent-graft surveillance. We discuss early generation stent-grafts, type III endoleak treatment options and the current long-term data for late EVAR-related complications. CONCLUSION: For patients who had undergone EVAR, type III endoleaks can present only decades later and pose a significant risk of aneurysmal rupture.
ABSTRACT
INTRODUCTION: Helical rim keloids occur commonly following ear piercings, trauma and previous surgeries and can be disfiguring. Many techniques have been developed to treated these disfiguring lesions with varying successes, however, individuals prone to developing keloids inadvertently recur despite best efforts. OBJECTIVE: To determine whether helical rim advancement flap reconstruction following helical rim keloid excision can reduce recurrences. DESIGN: Case series followed up to 2 years. SETTING: Single Centre Tertiary Hospital Facial Plastics Service. PARTICIPANTS: All patients who consented to helical rim advancement reconstruction after keloid excision. RESULTS: The authors report a series of 7 patients with helical rim keloids ranging from 1.2 cm to 5 cm in widest diameter treated with keloid excision and reconstruction with helical rim advancement flap technique. There were no recurrences within a mean of about 19 months post-operatively. Most patients report satisfaction with the cosmetic end-result. DISCUSSION: From the authors' experience, helical rim advancement reconstruction following excision of keloids about 2.5 cm in widest diameter is an excellent tension-free option to avoid recurrence of helical rim keloids. Wound tension is a key risk factor for keloid formation. We hypothesise that the reason why there was no recurrence is because in helical rim advancement flap reconstruction, the underlying helical rim takes all the tension of closure off the dermis, resulting in tension-free skin closure. CONCLUSION: Helical rim advancement flap reconstruction is a viable technique to avoid recurrence and minimise cosmetic deformities of the pinna for selected helical rim keloids.
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Caudal septal deviation leads to unfavorable esthetic as well as functional effects on the nasal airway. A modification to the tongue-in-groove (TIG) technique to correct these caudal septal deformities is described. With placement of a temporary suspension suture to the caudal septum, manual traction is applied, assuring that the caudal septum remains in the midline position while it is being secured with multiple through-and-through, trans-columellar and trans-septal sutures. From 2003 to 2016, 148 patients underwent endonasal septoplasty using this modified technique, with excellent functional and cosmetic outcomes and a revision rate of 1.4%. This modified TIG technique replaces the periosteal suture that secures the caudal septum to the midline nasal crest in the original TIG technique. This simplifies the procedure and minimizes the risk of securing the caudal septum off-midline when used in endonasal septoplasty.
Subject(s)
Nasal Septum/surgery , Rhinoplasty/methods , Suture Techniques , Adult , Esthetics , Female , Humans , Male , Reoperation/statistics & numerical data , Traction , Treatment OutcomeABSTRACT
Background: The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection. Methods: A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100ß, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared. Results: Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg-1 h-1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min-1 m-2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P<0.05). Conclusions: During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol. Clinical trial registration: NCT02113358.
Subject(s)
Fluid Therapy/methods , Intraoperative Care/methods , Stroke Volume/physiology , Supratentorial Neoplasms/surgery , Brain/surgery , Female , Humans , Male , Middle Aged , Single-Blind Method , Treatment OutcomeABSTRACT
BACKGROUND: Depression is prevalent among patients with late life neurocognitive disorders but its role as an independent risk factor is not established. We aimed to examine the longitudinal relationship between depression and the incidence of mild neurocognitive disorders (NCD) in a Chinese population. METHODS: We analyzed data from 889 community-living Chinese elderly in the Singapore Longitudinal Aging Study (SLAS) cohort. All subjects were cognitively normal at baseline based on their performance on the Mini-Mental State Examination (MMSE). Depression was defined as total score of 5 or more on the 15-item Geriatric Depression Scale. Incident cases of mild NCD were ascertained at follow up after an average of 45 moths (range: 10-62). Odds ratios (OR) of associations were calculated in logistic regression models that adjusted for potential confounders. RESULTS: A total of 59 mild NCD cases were identified. Increased risk of mild NCD was observed for subjects who had depressive symptom at baseline (OR=2.56, 95%CI 1.17-5.60) after controlling for age, gender, education, hypertension, diabetes mellitus, heart disease, APOE genotype and length of follow-up. The interaction between depression and APOE genotype was not statistically significant. CONCLUSION: Depressive symptom was independently associated with increased risk of mild NCD among Chinese elderly. Effective management of late life depression may potentially reduce incident cases of NCD in the population.
Subject(s)
Asian People , Cognition Disorders/epidemiology , Depression/epidemiology , Aged , Cognition Disorders/etiology , Depression/complications , Female , Follow-Up Studies , Humans , Incidence , Independent Living , Logistic Models , Longitudinal Studies , Male , Middle Aged , Prevalence , Prospective Studies , Reproducibility of Results , Risk Factors , Singapore , Surveys and QuestionnairesABSTRACT
AIMS: Erythropoietin (EPO), the key hormone involved in erythropoiesis, beneficially affects endothelial cells (ECs), but the detailed mechanisms are yet to be completely understood. In this study, we investigated the role of transient receptor potential vanilloid type 1 (TRPV1), a ligand-gated non-selective calcium (Ca2+ ) channel, in EPO-mediated endothelial nitric oxide synthase (eNOS) activation and angiogenesis. METHODS AND RESULTS: In ECs, EPO time dependently increased intracellular levels of calcium; this increase was abrogated by the Ca2+ chelators and pharmacological inhibitors of TRPV1 in bovine aortic ECs (BAECs) and TRPV1-transfected HEK293 cells. In addition, EPO-induced nitrite oxide (NO) production, phosphorylation of eNOS, Akt and AMP-activated protein kinase (AMPK) and the formation of TRPV1-Akt-AMPK-eNOS complex as well as tube formation were diminished by the pharmacological inhibition of TRPV1 in BAECs. Moreover, EPO time dependently induced the phosphorylation of phospholipase C-γ1 (PLC-γ1). Inhibition of PLC-γ1 activity blunted the EPO-induced Ca2+ influx, eNOS phosphorylation, TRPV1-eNOS complex formation and NO production. The phosphorylated level of eNOS increased in the aortas of EPO-treated wild-type (WT) mice or EPO-transgenic (Tg) mice but not in those of EPO-treated TRPV1-deficient (TRPV1-/- ) mice or EPO-Tg/TRPV1-/- mice. Matrigel plug assay showed that EPO-induced angiogenesis was abrogated in TRPV1 antagonist capsazepine-treated WT mice and TRPV1-/- mice. CONCLUSION: These findings indicate the EPO-induced Ca2+ influx via the activation of the PLC-γ1 signalling pathway, which leads to TRPV1 activation and consequently increases the association of the TRPV1-Akt-AMPK-eNOS complex, eNOS activation, NO production and angiogenesis.
Subject(s)
Enzyme Activation/physiology , Erythropoietin/metabolism , Neovascularization, Physiologic/physiology , Nitric Oxide Synthase Type III/metabolism , TRPV Cation Channels/metabolism , Animals , Cattle , Endothelial Cells/metabolism , Enzyme Activation/drug effects , Erythropoietin/pharmacology , HEK293 Cells , Humans , Immunoprecipitation , Mice , Mice, Inbred C57BL , Mice, TransgenicABSTRACT
OBJECTIVES: To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. DESIGN: Population-based longitudinal study. SETTING: The Singapore Longitudinal Aging Study (SLAS). PARTICIPANTS: 957 community-living Chinese elderly who were cognitively intact at baseline. MEASUREMENTS: We collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010. Odds ratio (OR) of association were calculated in logistic regression models that adjusted for potential confounders. RESULTS: A total of 72 incident NCD cases were identified from the cohort. Tea intake was associated with lower risk of incident NCD, independent of other risk factors. Reduced NCD risk was observed for both green tea (OR=0.43) and black/oolong tea (OR=0.53) and appeared to be influenced by the changing of tea consumption habit at follow-up. Using consistent non-tea consumers as the reference, only consistent tea consumers had reduced risk of NCD (OR=0.39). Stratified analyses indicated that tea consumption was associated with reduced risk of NCD among females (OR=0.32) and APOE ε4 carriers (OR=0.14) but not males and non APOE ε4 carriers. CONCLUSION: Regular tea consumption was associated with lower risk of neurocognitive disorders among Chinese elderly. Gender and genetic factors could possibly modulate this association.
Subject(s)
Neurocognitive Disorders/epidemiology , Neurocognitive Disorders/prevention & control , Tea , Aged , Apolipoprotein E4/blood , Asian People , Biomarkers/blood , Female , Follow-Up Studies , Humans , Incidence , Logistic Models , Longitudinal Studies , Male , Middle Aged , Risk Factors , Singapore/epidemiologyABSTRACT
Achievement of the optimal hydropower generation from operation of water reservoirs, is a complex problems. The purpose of this study was to formulate and improve an approach of a genetic algorithm optimization model (GAOM) in order to increase the maximization of annual hydropower generation for a single reservoir. For this purpose, two simulation algorithms were drafted and applied independently in that GAOM during 20 scenarios (years) for operation of Mosul reservoir, northern Iraq. The first algorithm was based on the traditional simulation of reservoir operation, whilst the second algorithm (Salg) enhanced the GAOM by changing the population values of GA through a new simulation process of reservoir operation. The performances of these two algorithms were evaluated through the comparison of their optimal values of annual hydropower generation during the 20 scenarios of operating. The GAOM achieved an increase in hydropower generation in 17 scenarios using these two algorithms, with the Salg being superior in all scenarios. All of these were done prior adding the evaporation (Ev) and precipitation (Pr) to the water balance equation. Next, the GAOM using the Salg was applied by taking into consideration the volumes of these two parameters. In this case, the optimal values obtained from the GAOM were compared, firstly with their counterpart that found using the same algorithm without taking into consideration of Ev and Pr, secondly with the observed values. The first comparison showed that the optimal values obtained in this case decreased in all scenarios, whilst maintaining the good results compared with the observed in the second comparison. The results proved the effectiveness of the Salg in increasing the hydropower generation through the enhanced approach of the GAOM. In addition, the results indicated to the importance of taking into account the Ev and Pr in the modelling of reservoirs operation.
ABSTRACT
Reduction malarplasty surgery has become increasingly popular in recent years, especially in many East Asian countries. This is, in part, because many Asians consider a small, smooth, and feminine face to be more attractive and aesthetically desirable. Among the various reduction malarplasty methods, the L-shaped osteotomy technique, through intraoral and sideburn incisions, is now one of the most frequently performed surgical techniques. During the surgical procedure, it is important to shave the zygomatic process of the temporal bone through the sideburn incision. By carrying out this simple adjunctive procedure, several remarkable results can be achieved. The facial width is reduced, especially in those patients with protrusion of the posterior portion of the arch. The outward curvature of the zygomatic arch is changed to point inward. And finally, the bony step that originates from the medial repositioning of the zygomatic arch is reduced, resulting in decreased palpability.
Subject(s)
Osteotomy/methods , Zygoma/surgery , Asian People , Face , Female , Humans , Photography , Radiography , Young Adult , Zygoma/diagnostic imagingABSTRACT
Taiwan had been considered rabies free since 1961. In 2013, Taiwan confirmed the detection of rabies virus in wild Taiwan ferret-badgers. Up to December 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. Genetic analysis indicates that TFBV is distinct from all other known rabies virus variants. To date, ferret-badger rabies is known to occur only in China and Taiwan. The temporal dynamics of rabid ferret-badgers in Taiwan suggests that the epizootic appears to have subsided to enzootic levels as of December 2014. According to the current epidemiologic data, there is only one TFBV strain in Taiwan. TFBV is still sequestered to the mountainous regions. Humans are at risk mainly through exposure to the virus from infected domestic meso-carnivores, mainly dogs and cats. Dogs and cats should be vaccinated to establish an immunological barrier to stop the spread of the disease from mountainous regions to domestic meso-carnivores.
Subject(s)
Disease Reservoirs/veterinary , Mustelidae/virology , Public Health Administration , Rabies virus/isolation & purification , Rabies/veterinary , Animals , Cat Diseases/prevention & control , Cats , Disease Outbreaks/veterinary , Dog Diseases/prevention & control , Dogs , Humans , Population Surveillance , Prevalence , Rabies/epidemiology , Rabies/prevention & control , Rabies Vaccines/immunology , Taiwan/epidemiologyABSTRACT
Bacteria capable of degrading polyhydroxyalkanoates (PHA) by secreting extracellular depolymerase enzymes were isolated from water and soil samples collected from various environments in Malaysia. A total of 8 potential degraders exhibited clear zones on poly(3-hydroxybutyrate) [P(3HB)] based agar, indicating the presence of extracellular PHA depolymerase. Among the isolates, DP5 exhibited the largest clearing zone with a degradation index of 6.0. The highest degradation activity of P(3HB) was also observed with depolymerase enzyme of DP5 in mineral salt medium containing P(3HB). Based on biochemical characterization and 16S rRNA cloning and sequencing, isolate DP5 was found to belong to the genus Acidovorax and subsequently named as Acidovorax sp. DP5. The highest extracellular depolymerase enzyme activity was achieved when 0.25% (w/v) of P(3HB) and 1 g/L of urea were used as carbon and nitrogen source, respectively, in the culture media. The most suitable assay condition of the depolymerase enzyme in response to pH and temperature was tested. The depolymerase produced by strain Acidovorax sp. DP5 showed high percentage of degradation with P(3HB) films in an alkaline condition with pH 9 and at a temperature of 40°C.
ABSTRACT
Clinical application of small interfering RNA (siRNA) in cancer therapy has been limited by the lack of an efficient systemic siRNA delivery system. In this report we describe an efficient siRNA delivery system directed to metastasized tumors, especially in the lungs. Anticancer siRNA was condensed in the presence of 9-arginine peptides (9Arg) and then complexed with cationic O,O'-dimyristyl-N-lysyl glutamate liposomes conjugated to antibodies against the epidermal growth factor receptor (EGFR). The ternary complex of optimized anti-EGFR-9Arg-lipoplexes exhibited efficient siRNA transfection of LS174T-Luc cancer cells grown in culture or orthotopically in mouse lungs. Anti-tumor Bcl-2/survivin siRNAs loaded in the anti-EGFR-9Arg-lipoplexes effectively suppressed transcription of their target genes, resulting in an efficient cancer cell death. Repeated intravenous administrations of the anti-EGFR-9Arg-lipoplexes effectively inhibited tumor growth in the mouse lungs and prolonged survival of the mice compared with nontargeted lipoplexes. These results suggest that the ternary complexes of anti-EGFR-9Arg-lipoplexes might have clinical applications in RNA interference cancer therapy.
Subject(s)
ErbB Receptors/metabolism , Inhibitor of Apoptosis Proteins/genetics , Lung Neoplasms/therapy , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Small Interfering/genetics , Animals , Cell Line, Tumor , Disease Progression , Female , Gene Expression , Gene Knockdown Techniques , Genetic Therapy , Humans , Inhibitor of Apoptosis Proteins/biosynthesis , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Radiography , Survivin , TransfectionABSTRACT
The availability of empirical data from human studies in recent years have lend credence to the old axiomatic wisdom that health benefits of tea drinking extend to the area of cognition. Specifically, there is increasing interest as to whether tea drinking can delay or even prevent the onset of Alzheimer's disease (AD). Data from several cross-sectional studies have consistently shown that tea drinking is associated with better performance on cognitive tests. This association is supported by longitudinal data from the Singapore Longitudinal Aging Study, the Chinese Longitudinal Healthy Longevity Survey and the Cardiovascular Health Study. The only two published longitudinal analyses on clinical outcome reported conflicting results: one study reported that mid-life tea drinking was not associated with risk reduction of Alzheimer's disease in late life while the other one found that green tea consumption reduced the incidence of dementia or mild cognitive impairment. Two small trials from Korea and Japan reported encouraging but preliminary results. While the existing evidence precludes a definite conclusion as to whether tea drinking can be an effective and simple lifestyle preventive measure for AD, further research involving longer-term longitudinal studies and randomized controlled trials is clearly warranted to shed light on this topic of immense public health interest. Biological markers of tea consumption and Alzheimer diseases should be employed in future research to better delineate the underlying mechanisms of tea drinking's protective effect on cognition.