Development, Validation and Field Evaluation of the Singapore Longitudinal Ageing Study (SLAS) Risk Index for Prediction of Mild Cognitive Impairment and Dementia.

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.

Nutritional Status and Risks of Cognitive Decline and Incident Neurocognitive Disorders: Singapore Longitudinal Ageing Studies.

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.

Tranexamic acid in traumatic brain injury.

BACKGROUND: Some surgeons advocate the usage of tranexamic acid (TXA) in traumatic brain injury (TBI). The aim of this study is to determine the effectiveness and safety of TXA in improving the outcome of TBI patients and in reducing the rate of clot expansion and mortality in TBI as compared to those without TXA. METHODS: This is a prospective observational cohort study conducted in Sarawak General Hospital, Malaysia. Patients 12 years of age and older with mild to severe TBI who had a brain computed tomography (CT) done within eight hours of injury were enrolled in the study. A total of 334 patients were recruited from the 5th of August 2016 until the 8th of March 2018 in Sarawak General Hospital. In all 167 of them were administered with TXA and another 167 of the patients were not. The primary outcome expected is the number of good outcomes in isolated TBI patients given TXA. Good outcome is defined by Glasgow Outcome Score-Extended (GOSE) of five and above. Secondary outcome was clot expansion of an intracranial bleed seen on the first scan that had expanded by 25% or more on any dimension on the second scan. RESULTS: The TXA did not show significant trend of good outcome in terms of GOSE (p=0.763). However, for moderate and severe acute subdural haemorrhage (SDH) subgroups, there was a significant difference (p=0.042). Clot expansion was present in 14 patients (12.7%) with TXA given and in 54 patients (38.8%) without TXA. The difference was statistically significant (p<0.001). Of the patients who received TXA, there was one case (0.6%) of deep vein thrombosis. Apart from that, TXA showed non-significant trend in reducing mortality (p=0.474). CONCLUSIONS: Tranexamic acid reduces the rate of clot expansion in TBI by 26.1% (38.8-12.7%) without significantly increasing the risk of a thrombotic event. It can also improve the outcome of moderate and severe TBI patients with acute SDH.

Lactobacillus plantarum DR7 improved brain health in aging rats via the serotonin, inflammatory and apoptosis pathways.

Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of Lactobacillus plantarum DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and L. plantarum DR7 (109 cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats (P<0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of TPH1 in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging.

Risk Factors of Progression to Frailty: Findings from the Singapore Longitudinal Ageing Study.

OBJECTIVES: To investigate risk factors of incident physical frailty. DESIGN: A population-based observational longitudinal study. SETTING: Community-dwelling elderly with age 55 years and above recruited from 2009 through 2011 in the second wave Singapore Longitudinal Ageing Study-2 (SLAS-2) were followed up 3-5 years later. PARTICIPANTS: A total of 1297 participants, mean age of 65.6 ±0.19, who were free of physical frailty. MEASUREMENTS: Incident frailty defined by three or more criteria of the physical phenotype used in the Cardiovascular Health Study was determined at follow-up. Potential risk factors assessed at baseline included demographic, socioeconomic, medical, psychological factors, and biochemical markers. RESULTS: A total of 204 (15.7%) participants, including 81 (10.87%) of the robust and 123 (22.28%) of the prefrail transited to frailty at follow-up. Age, no education, MMSE score, diabetes, prediabetes and diabetes, arthritis, ≥5 medications, fair and poor self-rated health, moderate to high nutritional risk (NSI ≥3), Hb (g/dL), CRP (mg/L), low B12, low folate, albumin (g/L), low total cholesterol, adjusted for sex, age and education, were significantly associated (p<0.05) with incident frailty. In stepwise selection models, age (year) (OR=1.07, 95%CI=1.03-1.10, p<0.001), albumin (g/L) (OR=0.85, 95%CI=0.77-0.94, p=0.002), MMSE score (OR=0.88, 95%CI=0.78-0.98, p=0.02), low folate (OR=3.72, 95%CI=1.17-11.86, p=0.03, and previous hospitalization (OR=2.26, 95%CI=1.01-5.04,p=0.05) were significantly associated with incident frailty. CONCLUSIONS: The study revealed multiple modifiable risk factors, especially related to poor nutrition, for which preventive measures and early management could potentially halt or delay the development of frailty.

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats.

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

A pilot study of cardiopulmonary exercise testing and cardiac stress positron emission tomography before major non-cardiac surgery.

Cardiac events are a common cause of peri-operative morbidity. Cardiopulmonary exercise testing can objectively assess risk, but it does not quantify myocardial ischaemia. With appropriate dietary preparation to suppress basal myocardial glucose uptake, positron emission tomography with 18 F-fluorodeoxyglucose can identify post-ischaemic myocardium, providing an attractive complement to exercise testing. We aimed to investigate the feasibility of this diagnostic algorithm. Patients referred for cardiopulmonary exercise testing before major cancer surgery were prospectively recruited. Exercise testing and positron emission tomography imaging were performed after a high fat-low carbohydrate meal. Protocol feasibility (primary end-point) included compliance with pre-test diet instructions and the completion of tests. Stress myocardial perfusion imaging was performed if either exercise testing or positron emission tomography was equivocal or positive for ischaemia. We recorded cardiac complications for 30 postoperative days. We enrolled 26 participants, 20 of whom completed protocol. Twenty-one participants proceeded to surgery: myocardial injury or infarction was diagnosed in three participants, two of whom had positive or equivocal positron emission tomography but negative myocardial perfusion imaging. We have shown that pre-operative cardiac positron emission tomography after cardiopulmonary exercise testing is feasible; protocol deviations were minor and did not affect image quality. Our findings warrant further investigation to compare the diagnostic utility of cardiac positron emission tomography imaging with standard pre-operative stress tests.

Molecular basis for the production of cyclic peptides by plant asparaginyl endopeptidases.

Asparaginyl endopeptidases (AEPs) are proteases that have crucial roles in plant defense and seed storage protein maturation. Select plant AEPs, however, do not function as proteases but as transpeptidases (ligases) catalyzing the intra-molecular ligation of peptide termini, which leads to peptide cyclization. These ligase-type AEPs have potential biotechnological applications ranging from in vitro peptide engineering to plant molecular farming, but the structural features enabling these enzymes to catalyze peptide ligation/cyclization rather than proteolysis are currently unknown. Here, we compare the sequences, structures, and functions of diverse plant AEPs by combining molecular modeling, sequence space analysis, and functional testing in planta. We find that changes within the substrate-binding pocket and an adjacent loop, here named the "marker of ligase activity", together play a key role for AEP ligase efficiency. Identification of these structural determinants may facilitate the discovery of more ligase-type AEPs and the engineering of AEPs with tailored catalytic properties.

Characterization of isolated liver sinusoidal endothelial cells for liver bioengineering.

BACKGROUND: The liver sinusoidal capillaries play a pivotal role in liver regeneration, suggesting they may be beneficial in liver bioengineering. This study isolated mouse liver sinusoidal endothelial cells (LSECs) and determined their ability to form capillary networks in vitro and in vivo for liver tissue engineering purposes. METHODS AND RESULTS: In vitro LSECs were isolated from adult C57BL/6 mouse livers. Immunofluorescence labelling indicated they were LYVE-1+/CD32b+/FactorVIII+/CD31-. Scanning electron microscopy of LSECs revealed the presence of characteristic sieve plates at 2 days. LSECs formed tubes and sprouts in the tubulogenesis assay, similar to human microvascular endothelial cells (HMEC); and formed capillaries with lumens when implanted in a porous collagen scaffold in vitro. LSECs were able to form spheroids, and in the spheroid gel sandwich assay produced significantly increased numbers (p = 0.0011) of capillary-like sprouts at 24 h compared to HMEC spheroids. Supernatant from LSEC spheroids demonstrated significantly greater levels of vascular endothelial growth factor-A and C (VEGF-A, VEGF-C) and hepatocyte growth factor (HGF) compared to LSEC monolayers (p = 0.0167; p = 0.0017; and p < 0.0001, respectively), at 2 days, which was maintained to 4 days for HGF (p = 0.0017) and VEGF-A (p = 0.0051). In vivo isolated mouse LSECs were prepared as single cell suspensions of 500,000 cells, or as spheroids of 5000 cells (100 spheroids) and implanted in SCID mouse bilateral vascularized tissue engineering chambers for 2 weeks. Immunohistochemistry identified implanted LSECs forming LYVE-1+/CD31- vessels. In LSEC implanted constructs, overall lymphatic vessel growth was increased (not significantly), whilst host-derived CD31+ blood vessel growth increased significantly (p = 0.0127) compared to non-implanted controls. LSEC labelled with the fluorescent tag DiI prior to implantation formed capillaries in vivo and maintained LYVE-1 and CD32b markers to 2 weeks. CONCLUSION: Isolated mouse LSECs express a panel of vascular-related cell markers and demonstrate substantial vascular capillary-forming ability in vitro and in vivo. Their production of liver growth factors VEGF-A, VEGF-C and HGF enable these cells to exert a growth stimulus post-transplantation on the in vivo host-derived capillary bed, reinforcing their pro-regenerative capabilities for liver tissue engineering studies.

Multi-Domains Lifestyle Interventions Reduces Depressive Symptoms among Frail and Pre-Frail Older Persons: Randomized Controlled Trial.

BACKGROUND: We investigated the effect of multi-domain lifestyle (physical, nutritional, cognitive) interventions among frail and pre-frail community-living older persons on reducing depressive symptoms. METHOD: Participants aged 65 and above were randomly allocated to 24 weeks duration interventions with nutritional supplementation (N=49), physical training (N=48), cognitive training (N=50), combination intervention (N=49) and usual care control (N=50). Depressive symptoms were assessed by the Geriatric Depression Scale (GDS-15) at baseline (0M), 3 month (3M), 6 month (6M) and 12 month (12M). RESULTS: Mean GDS scores in the control group increased from 0.52 (0M) and 0.54 (3M) to 0.74 (6M), and 0.83 (12M). Compared to the control group, interventions showed significant differences (∆=change) at 6M for cognitive versus control (∆=-0.39, p=0.021, group*time interaction p=0.14); physical versus control (∆ =-0.37, p=0.026, group*time interaction p=0.13), and at 12M for nutrition versus control (∆ =-0.46, p=0.016, group*time interaction p=0.15). The effect for combination versus control was significant at 6M (∆ =-0.43, p=0.020) and 12M (∆ =-0.51, p=0.005, group*time interaction p=0.026). Estimated 12-month cumulative incidence of depressive symptoms (GDS≥2) relative to control were OR=0.38, p=0.037 (nutrition); OR=0.71, p=0.40 (cognitive); OR=0.39, p=0.042 (physical training) and OR=0.38, p=0.037 (combination). Changes in gait speed and energy level were significantly associated with changes in GDS scores over time. CONCLUSION: Multi-domain interventions that reverse frailty among community-living older persons also reduce depressive symptomatology. Public health education and programmatic measures combining nutritional, physical and cognitive interventions for at-risk frail older people may likely benefit psychological wellbeing.

Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients.

Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach. Our study defines the functional kinetics of each TCRA and TCRB clone, and changes in T-cell diversity (with identification of CDR3 sequences) and the extent of clonal expansion of certain T-cells. Using this approach, our study demonstrates that higher percentage of cord-blood cells at 30 days after transplant was correlated with higher diversity of TCR repertoire, implicating the role of cord-chimerism in enhancing immune recovery. Importantly, we found that GVHD and relapse, exclusive of each other, were correlated with lower TCR repertoire diversity and expansion of certain T-cell clones. Our results highlight novel insights into the balance between GVHD and GVL effect, suggesting that higher diversity early after transplant possibly implies lower risks of both GVHD and relapse following the HSCT transplantation.

Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort.

BACKGROUND: Vitamin D status varies with geographic location and no studies of vitamin D in systemic lupus erythematosus (SLE) have been reported in the Southern Hemisphere. OBJECTIVES: To assess the prevalence of vitamin D deficiency in an Australian SLE cohort, and its relationship with disease activity. METHODS: Data were collected prospectively on 119 consecutive patients with SLE in the Monash Lupus Clinic in Melbourne, Australia, between January 2007 and January 2013. Patients had simultaneous serum 25-hydroxyvitamin D concentration and disease activity (SLEDAI-2K) recorded. Statistical methods were used to determine the correlation of serum vitamin D level and disease activity both at baseline and at a subsequent time point. Adjustments were made for the use of glucocorticoids, immunosuppressants and vitamin D supplementation. RESULTS: Vitamin D deficiency (<40 nmol/L) was detected in 27.7% of patients at baseline. Multiple regression analysis showed a significant inverse correlation of SLEDAI-2K with baseline vitamin D level and with vitamin D supplementation. Over a 12-month period of observation, among the 119 patients, there were 464 serial vitamin D measurements with corresponding SLEDAI-2K, representing 266 time intervals. The median change in vitamin D level was an increase of 25 nmol/L and this corresponded with a decline in SLEDAI-2K of 2 units. In regression analysis, there was a significant association between low vitamin D at a prior time point and a rise in SLEDAI-2K at the subsequent time point (univariable OR 3.3, 95% CI 1.5 to 7.7, p=0.005) or having a high disease activity (SLEDAI-2k>10) at the subsequent time point (univariable OR 3.1, 95% CI 1.4 to 6.8, p=0.004). CONCLUSIONS: In Australian patients with SLE, low vitamin D was associated with a higher disease activity and an increase in serum vitamin D was associated with reduced disease activity over time. The therapeutic effect of vitamin D in SLE should be further assessed in interventional studies.

Tea consumption and physical function in older adults: a cross-sectional study.

BACKGROUND: Tea consumption has been reported to be associated with lowered risk of cardiovascular disease, stroke and osteoporosis that cause functional disability, but its association with physical function has not been investigated directly. OBJECTIVE: We examined the association between tea consumption and performance in gait and balance, instrumental and basic activities of daily living (IADL and BADL) in a cross-sectional study of community-living older persons. METHOD: Baseline data of 2398 adults aged ≥ 55 years in the Singapore Longitudinal Ageing Studies who completed self-reported current tea consumption, Performance Oriented Mobility Assessment (POMA) of gait and balance, and self reports of BADL and IADL were analyzed. RESULTS: In multivariate analyses controlling for age, gender, education, housing type, co-morbidities, hospitalization, arthritis and hip fracture, GDS depression score, MMSE cognitive score, body mass index, creatinine, serum albumin, haemoglobin, physical activities score and coffee consumption, tea consumption was positively associated with better balance (ß=0.06, p<0.01), gait (ß=0.01, p=0.02), IADL (ß=0.03, p=0.01) and BADL (ß=0.01, p=0.05). Strongly positive associations were observed for black/oolong tea in multivariate analyses, and for green tea consumption only in univariate analysis, whereas coffee consumption was not associated at all. CONCLUSIONS: Tea consumption was associated with better physical functional performances in community-living older adults.

Plasma progesterone changes and length of oestrous cycle in Rusa Deer (Rusa timorensis).

A study was conducted to profile the plasma progesterone (P4) concentrations and establish the length of oestrous cycle in the Rusa timorensis during the breeding season. Five healthy hinds were selected for peripheral blood sampling twice weekly to gauge the P4 levels by radioimmunoassay, at the start of the breeding season indicated by rutting behaviours of sexually active males. The hinds were polyestrous as proven by the cyclic trend of P4 levels. After the presumptive oestrus indicated by the lowest P4 concentrations (0.20±0.09ng/ml), this ovarian hormone was markedly elevated on day 7 of the cycle (0.78±0.20ng/ml), reached its peak (2.61±0.23ng/ml, P<0.05) on day 14, and then declined to the basal level in the subsequent oestrus. The mean oestrous cycle length in R. timorensis during the breeding season was 19.2 days with a range of 18-21 days, and the pattern of circulating progesterone during the oestrous cycle of the R. timorensis is similar to those of other deer species. It was also observed that the length of oestrous cycle of R. timorensis determined by gauging the progesterone levels and observation of the oestrous behaviours as well as changes in the cellular pattern of vaginal epithelial cells are highly consistent.

An unusual localised reaction associated with vancomycin therapy.

Vancomycin has been documented to cause various adverse cutaneous reactions. We present a case report of a man, who developed a large localized erythematous plaque in his forearm following parenteral vancomycin therapy. We believe this to be the first reported case of such cutaneous reaction associated with parenteral vancomycin therapy.

Multicentre survey of radiologically inserted gastrostomy feeding tube (RIG) in the UK.

AIMS: To evaluate the variance in current UK clinical practice and clinical outcomes for direct percutaneous radiologically inserted gastrostomy (RIG). MATERIALS AND METHODS: A prospective UK multicentre survey of RIG performed between October 2008 and August 2010 was performed through the British Society of Gastrointestinal and Abdominal Radiology (BSGAR). RESULTS: Data from 684 patients were provided by 45 radiologists working at 17 UK centres. Two hundred and sixty-three cases (40%) were performed with loop-retained catheters, and 346 (53%) with balloon-retained devices. Sixty percent of all patients experienced pain in the first 24 h, but settled in the majority thereafter. Early complications, defined as occurring in the first 24 h, included minor bleeding (1%), wound infection (3%), peritonism (2%), and tube misplacement (1%). Late complications, defined as occurring between day 2 and day 30 post-procedure, included mild pain (30%), persisting peritonism (2%), and 30 day mortality of 1% (5/665). Pre-procedural antibiotics or anti-methicillin-resistant Staphylococcus aureus (MRSA) prophylaxis did not affect the rate of wound infection, peritonitis, post-procedural pain, or mortality. Ninety-three percent of cases were performed using gastropexy. Gastropexy decreased post-procedural pain (p < 0.001), but gastropexy-related complications occurred in 5% of patients. However, post-procedure pain increased with the number of gastropexy sutures used (p < 0.001). The use of gastropexy did not affect the overall complication rate or mortality. Post-procedure pain increased significantly as tube size increased (p < 0.001). The use of balloon-retention feeding tubes was associated with more pain than the deployment of loop-retention devices (p < 0.001). CONCLUSION: RIG is a relatively safe procedure with a mortality of 1%, with or without gastropexy. Pain is the commonest complication. The use of gastropexy, fixation dressing or skin sutures, smaller tube sizes, and loop-retention catheters significantly reduced the incidence of pain. There was a gastropexy-related complication rate in 5% of patients. Neither pre-procedural antibiotics nor anti-MRSA prophylaxis affected the rate of wound infection.

Factors related to choosing psychiatry as a future medical career among medical students at the Faculty of Medicine of the University of Indonesia.

OBJECTIVE. To identify factors related to choosing psychiatry as a future medical career and attitude towards psychiatry among medical students of the International Class Programme of the Faculty of Medicine, The University of Indonesia. METHODS. This was a cross-sectional design which included 225 data sets from first to sixth year medical students (n = 188) as well as the freshly graduated medical doctors (n = 37). The Attitude Towards Psychiatry-30 questionnaire (ATP-30) was adopted. Data including demographics, past experience in psychiatry, inclination to work in psychiatry, and 3 specialty choices for future medical career were collected. Independent t test and logistic regression were used in data analysis. RESULTS. The mean ATP-30 score from the fresh graduates was slightly higher compared with the medical students. Inclination to work in the field of psychiatry, past experience in psychiatry, and the ATP-30 score were significantly correlated and contributed 57% to the prediction of choosing psychiatry as a future medical career (p < 0.05). CONCLUSION. The greater inclination to work in the field of psychiatry, as well as a better attitude towards psychiatry can predict the choice of psychiatry as a future medical career. Therefore, it is very important to increase the quality of psychiatry teaching and to motivate medical students who show a high level of interest in psychiatry.

NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the HMGB1-mediated autophagic response.

Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, is known to have important roles in proliferation and growth of tumor cells and in chemotherapy resistance. Yet, the mechanisms underlying how NAC1 contributes to drug resistance remain largely unclear. We report here that autophagy was involved in NAC1-mediated resistance to cisplatin, a commonly used chemotherapeutic drug in the treatment of ovarian cancer. We found that treatment with cisplatin caused an activation of autophagy in ovarian cancer cell lines, A2780, OVCAR3 and SKOV3. We further demonstrated that knockdown of NAC1 by RNA interference or inactivation of NAC1 by inducing the expression of a NAC1 deletion mutant that contains only the BTB/POZ domain significantly inhibited the cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity. Moreover, inhibition of autophagy and sensitization to cisplatin by NAC1 knockdown or inactivation were accompanied by induction of apoptosis. To confirm that the sensitizing effect of NAC1 inhibition on the cytotoxicity of cisplatin was attributed to suppression of autophagy, we assessed the effects of the autophagy inhibitors 3-methyladenosine and chloroquine, and small interfering RNAs (siRNAs) targeting beclin 1 or Atg5 on the cytotoxicity of cisplatin. Treatment with 3-methyladenosine, chloroquine or beclin 1 and Atg5-targeted siRNA also enhanced the sensitivity of SKOV3, A2780 and OVCAR3 cells to cisplatin, indicating that suppression of autophagy indeed renders tumor cells more sensitive to cisplatin. Regulation of autophagy by NAC1 was mediated by the high-mobility group box 1 (HMGB1), as the functional status of NAC1 was associated with the expression, translocation and release of HMGB1. The results of our study not only revealed a new mechanism determining cisplatin sensitivity but also identified NAC1 as a novel regulator of autophagy. Thus, the NAC1-mediated autophagy may be exploited as a new target for enhancing the efficacy of cisplatin against ovarian cancer and other types of malignancies.

Serum albumin and hemoglobin are associated with physical function in community-living older persons in Singapore.

OBJECTIVES: Albumin and hemoglobin are viewed as markers of nutritional and inflammatory status. This study examined the associations of serum albumin and hemoglobin with physical function in community-living older adults. DESIGN: Population-based cross-sectional and longitudinal study. SETTING: The Singapore Longitudinal Aging Studies (SLAS), a community-based study in urban Singapore. PARTICIPANTS: 2762 older adults aged 55 and above assessed at baseline, and 1829 at follow up 1-2 years later. MEASUREMENTS: Serum albumin and hemoglobin, Performance Oriented Mobility Assessment (POMA), knee extension strength at baseline, and Instrumental Activities of Daily Living (IADL) at baseline and follow up. RESULTS: In cross-sectional multivariate analyses that adjusted for haemoglobin and other confounders, albumin showed a significant linear association (p<0.001) with POMA balance score (b=0.06, SE=0.02) and knee extension strength (b=0.70, SE=0.10). Independently of albumin, hemoglobin also showed a significant linear association with POMA balance score (b=0.09, SE=0.04). In longitudinal analyses, albumin was significantly associated with IADL decline (IADL total score drop>=1 during follow-up), OR= 0.92 (0.87 - 0.97), p=<0.01. CONCLUSION: The findings suggest that low levels of albumin and hemoglobin are potentially useful risk markers of physical functional decline in older adults. Further research should investigate whether improvements in the levels of albumin and hemoglobin alter the level of functional disability and risk of functional decline.