Normative reference values, determinants and regression equations for the incremental shuttle walk test (ISWT) in healthy Asian population aged 21 to 80 years.

BACKGROUND: The validated Incremental Shuttle Walk Test (ISWT) is widely used for evaluating maximal exercise capacity, with the distance-walked (IWSD) as the primary outcome. However, there are no normative reference values (NRV) and reference equations to predict ISWD for the Singaporean population. OBJECTIVES: This study aims to establish the NRV and reference equations for ISWD in healthy Singaporeans aged 21 to 80 and investigate the determining variables during ISWT. METHODS: This cross-sectional study recruited community-dwelling healthy subjects aged 21-80 from the community via convenience sampling. Each subject completed two trials of the ISWT according to the standard protocol. Variables measured during the trials included ISWD, pre-and post-test heart rate (HR), oxygen saturation, blood pressure (BP), modified Borg's dyspnoea score and Borg's rate of perceived exertion (RPE). RESULTS: 199 healthy Singaporean (females = 114, males = 85) participated in the study. The overall median ISWD was 660.0 metres (m) [interquartile range (IQR):440.0-850.0]. The age-stratified mean ISWD ranged from 430.0 m (IQR:350.0-450.0) (aged 60-80) to 480.0 m (IQR:438.0-650.0) (aged 40-59) to 780.0 m (IQR:670.0-960.0) (aged 21-39). Gender, age, weight, height and HR change (highest post-test HR minus pre-test HR) were the most significant variables (p < 0.001). IWSD (m) = 651.4(Height, m) +89.7(Gender, male = 1; female = 0) -6.31(Age, years) -3.61(Weight, kilograms) +2.54(HR change, beats per minute); R2 = 0.741. Previously published ISWT reference equations cannot accurately predict the ISWD in the Singaporean population. CONCLUSIONS: This study investigated the ISWD NRV and established reference equations for healthy Singaporeans aged 21-80. The information would be beneficial in setting performance benchmarks to guide physical assessment, intervention and rehabilitation.

Ancient Lowland Maya neighborhoods: Average Nearest Neighbor analysis and kernel density models, environments, and urban scale.

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method-combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups-to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization.

Trends of chronic illness in emergency department admissions among elderly adults in a tertiary hospital over ten years.

BACKGROUND: This study aimed to determine to what extent an aging population and shift to chronic illness has contributed to emergency admissions at a tertiary care hospital over ten years. METHODS: This was a retrospective observational study performed using a database of all emergency admissions from the Emergency Department (ED) at a single tertiary hospital in Singapore during a ten-year period (January 1st, 2008 to December 31st, 2017). Emergency admissions were defined as ED visits with inpatient admission as the disposition. This study analyzed the trends of demographics, pre-existing comorbidities, chronic conditions or ambulatory care sensitive conditions (ACSC) of all patients who underwent emergency admissions in Singapore General Hospital. RESULTS: A total of 446,484 emergency records were included. For elderly patients, the proportions of them had pre-existing multimorbidity at the time of undergoing emergency admissions were found to be lower at the end the 10-year study period relative to the beginning of the study period. The proportions of emergency admissions whose ED primary diagnoses were categorized as chronic conditions and certain chronic ACSC including chronic obstructive pulmonary disease, congestive heart failure, diabetes complications, and epilepsy also decreased for elderly patients over the 10-year study period. CONCLUSIONS: In Singapore, despite a rapidly aging population, there have been surprisingly lower proportions of chronic conditions, pre-existing comorbidities, and chronic ACSC among the elderly emergency admissions. This is possibly consistent with an overall improved management of the chronic conditions among the elderly population. Future studies should include similar studies at the national level and comparison with other healthcare settings in different countries.

Robust Performance of Potentially Functional SNPs in Machine Learning Models for the Prediction of Atorvastatin-Induced Myalgia.

Statins can cause muscle symptoms resulting in poor adherence to therapy and increased cardiovascular risk. We hypothesize that combinations of potentially functional SNPs (pfSNPs), rather than individual SNPs, better predict myalgia in patients on atorvastatin. This study assesses the value of potentially functional single nucleotide polymorphisms (pfSNPs) and employs six machine learning algorithms to identify the combination of SNPs that best predict myalgia. Methods: Whole genome sequencing of 183 Chinese, Malay and Indian patients from Singapore was conducted to identify genetic variants associated with atorvastatin induced myalgia. To adjust for confounding factors, demographic and clinical characteristics were also examined for their association with myalgia. The top factor, sex, was then used as a covariate in the whole genome association analyses. Variants that were highly associated with myalgia from this and previous studies were extracted, assessed for potential functionality (pfSNPs) and incorporated into six machine learning models. Predictive performance of a combination of different models and inputs were compared using the average cross validation area under ROC curve (AUC). The minimum combination of SNPs to achieve maximum sensitivity and specificity as determined by AUC, that predict atorvastatin-induced myalgia in most, if not all the six machine learning models was determined. Results: Through whole genome association analyses using sex as a covariate, a larger proportion of pfSNPs compared to non-pf SNPs were found to be highly associated with myalgia. Although none of the individual SNPs achieved genome wide significance in univariate analyses, machine learning models identified a combination of 15 SNPs that predict myalgia with good predictive performance (AUC >0.9). SNPs within genes identified in this study significantly outperformed SNPs within genes previously reported to be associated with myalgia. pfSNPs were found to be more robust in predicting myalgia, outperforming non-pf SNPs in the majority of machine learning models tested. Conclusion: Combinations of pfSNPs that were consistently identified by different machine learning models to have high predictive performance have good potential to be clinically useful for predicting atorvastatin-induced myalgia once validated against an independent cohort of patients.

Health-seeking behaviour of foreign workers in Singapore: Insights from emergency department visits.

INTRODUCTION: Foreign workers (FWs) on work permit face unique health challenges and potential barriers to healthcare. We aimed to examine the epidemiology, attendance patterns, disposition, and adherence to follow-up, by FWs on work permit to two emergency departments (EDs) in Singapore. METHODS: In this retrospective observational study, we included consecutive FWs on work permit who registered at the EDs of two public restructured hospitals from 1 May 2016 to 31 October 2016. Data obtained from electronic medical records included patient demographics, triage acuity, disposition, ED diagnoses and bill information. RESULTS: There were 6,429 individual FWs on work permit who contributed to 7,157 ED visits over the 6-month study period, with male predominance (72.7%, 4672/6429), and median age of 31 (interquartile range 26 to 38) years. A high proportion of these FWs were triaged to low-acuity status compared to the general ED population (66.9% versus 45.9%, P<0.001). Trauma-related injuries contributed to 34.4% of their visits, and were more likely to result in admission compared to non-trauma-related conditions (18.7% vs 15.2%, P<0.001). FWs engaged in shipyard, construction and process industries were more likely to be discharged "against medical advice" (14.8% vs 3.2%, P<0.001), and default their specialist outpatient follow-up (50.1% vs 34.2%, P<0.001) for non-trauma-related conditions compared to trauma-related injuries. CONCLUSION: In Singapore, the EDs of public restructured hospitals provide healthcare safety nets to FWs on work permit. These workers made more low-acuity visits compared to the general population during the study period and may face potential barriers to admission and follow-up.

Health-seeking behaviour of foreign workers in Singapore: Insights from emergency department visits

INTRODUCTION@#Foreign workers (FWs) on work permit face unique health challenges and potential barriers to healthcare. We aimed to examine the epidemiology, attendance patterns, disposition, and adherence to follow-up, by FWs on work permit to two emergency departments (EDs) in Singapore.@*METHODS@#In this retrospective observational study, we included consecutive FWs on work permit who registered at the EDs of two public restructured hospitals from 1 May 2016 to 31 October 2016. Data obtained from electronic medical records included patient demographics, triage acuity, disposition, ED diagnoses and bill information.@*RESULTS@#There were 6,429 individual FWs on work permit who contributed to 7,157 ED visits over the 6-month study period, with male predominance (72.7%, 4672/6429), and median age of 31 (interquartile range 26 to 38) years. A high proportion of these FWs were triaged to low-acuity status compared to the general ED population (66.9% versus 45.9%, @*CONCLUSION@#In Singapore, the EDs of public restructured hospitals provide healthcare safety nets to FWs on work permit. These workers made more low-acuity visits compared to the general population during the study period and may face potential barriers to admission and follow-up.

Dockground Tool for Development and Benchmarking of Protein Docking Procedures.

Databases of protein-protein complexes are essential for the development of protein modeling/docking techniques. Such databases provide a knowledge base for docking algorithms, intermolecular potentials, search procedures, scoring functions, and refinement protocols. Development of docking techniques requires systematic validation of the modeling protocols on carefully curated benchmark sets of complexes. We present a description and a guide to the DOCKGROUND resource ( http://dockground.compbio.ku.edu ) for structural modeling of protein interactions. The resource integrates various datasets of protein complexes and other data for the development and testing of protein docking techniques. The sets include bound complexes, experimentally determined unbound, simulated unbound, model-model complexes, and docking decoys. The datasets are available to the user community through a Web interface.

Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

ERAIZDA: a model for holistic annotation of animal infectious and zoonotic diseases.

There is an urgent need for a unified resource that integrates trans-disciplinary annotations of emerging and reemerging animal infectious and zoonotic diseases. Such data integration will provide wonderful opportunity for epidemiologists, researchers and health policy makers to make data-driven decisions designed to improve animal health. Integrating emerging and reemerging animal infectious and zoonotic disease data from a large variety of sources into a unified open-access resource provides more plausible arguments to achieve better understanding of infectious and zoonotic diseases. We have developed a model for interlinking annotations of these diseases. These diseases are of particular interest because of the threats they pose to animal health, human health and global health security. We demonstrated the application of this model using brucellosis, an infectious and zoonotic disease. Preliminary annotations were deposited into VetBioBase database (http://vetbiobase.igbb.msstate.edu). This database is associated with user-friendly tools to facilitate searching, retrieving and downloading of disease-related information. Database URL: http://vetbiobase.igbb.msstate.edu.

Improving docking results via reranking of ensembles of ligand poses in multiple X-ray protein conformations with MM-GBSA.

There is a tendency in the literature to be critical of scoring functions when docking programs perform poorly. The assumption is that existing scoring functions need to be enhanced or new ones developed in order to improve the performance of docking programs for tasks such as pose prediction and virtual screening. However, failures can result from either sampling or scoring (or a combination of the two), although less emphasis tends to be given to the former. In this work, we use the programs GOLD and Glide on a high-quality data set to explore whether failures in pose prediction and binding affinity estimation can be attributable more to sampling or scoring. We show that identification of the correct pose (docking power) can be improved by incorporating ligand strain into the scoring function or rescoring an ensemble of diverse docking poses with MM-GBSA in a postprocessing step. We explore the use of nondefault docking settings and find that enhancing ligand sampling also improves docking power, again suggesting that sampling is more limiting than scoring for the docking programs investigated in this work. In cross-docking calculations (docking a ligand to a noncognate receptor structure) we observe a significant reduction in the accuracy of pose ranking, as expected and has been reported by others; however, we demonstrate that these alternate poses may in fact be more complementary between the ligand and the rigid receptor conformation, emphasizing that treating the receptor rigidly is an artificial constraint on the docking problem. We simulate protein flexibility by the use of multiple crystallographic conformations of a protein and demonstrate that docking results can be improved with this level of protein sampling. This work indicates the need for better sampling in docking programs, especially for the receptor. This study also highlights the variable descriptive value of RMSD as the sole arbiter of pose replication quality. It is shown that ligand poses within 2 Å of the crystallographic one can show dramatic differences in calculated relative protein-ligand energies. MM-GBSA rescoring of distinct poses overcomes some of the sensitivities of pose ranking experienced by the docking scoring functions due to protein preparation and binding site definition.

Resident surgical experience with lens and corneal refractive surgery: survey of the ASCRS Young Physicians and Residents Membership.

UNLABELLED: A 43-question survey was e-mailed to all resident members of the American Society of Cataract and Refractive Surgery (ASCRS), ASCRS members in practice for 5 or fewer years, and residency program directors of 118 U.S. Accreditation Council for Graduate Medical Education-accredited ophthalmology programs (for distribution to their residents) in June 2010. Two hundred eighty-five of 2279 surveys sent were completed and returned, for a response rate of 12.5%. Most respondents (88.7%) had served as primary surgeon in more than 100 cataract surgeries. Fifty-two percent of respondents had not performed corneal relaxing incisions; 60% had no experience implanting a toric IOL. Twenty-two percent had experience implanting a presbyopia-correcting IOL. Over 75% had not performed any corneal refractive surgical procedures. Although basic cataract case numbers appear adequate, there are significant perceived deficiencies in current resident training models for surgical astigmatism management, implanting presbyopia-correcting IOLs, and corneal refractive surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Chemotherapy: What is its role in meningioma?

While strong evidence exists for the standard therapy for meningiomas, inclusive of surgery and/or radiation therapy, for those tumors which recur, progress or are inoperable, the optimal medical therapies are yet to be elucidated. This article reviews the current literature for chemotherapeutic options for this subset of tumors, including cytotoxic agents, biologic agents, targeted molecular agents and hormonal agents. At this point in time, the most data is with hydroxyurea and somatostatin, although further trials with combination and targeted molecular therapies are still underway.

Recurrent Corneal Erosion Syndrome: A Study of 364 Episodes.

The purpose of the study was to investigate the management of recurrent corneal erosion syndrome (RES). A retrospective case series design was employed in which all RES cases presenting to the Duke University Eye Center from 1995 to 2002 were included. In total, 364 episodes of RES occurred in 261 patients during the study period. Of this 61% of patients were female (P < .001), average age was 46.0 years, and etiologies included trauma (51.3%), anterior basement membrane dystrophy (29.1%), other etiologies (10.3%) and unknown (9.2%). Treatments included conservative therapy (83.2%), anterior stromal puncture (ASP)(12.6%) and phototherapeutic keratectomy (PTK)(4.1%). Recurrence by treatment was 31.0% for conservative therapy, 23.9% for ASP and 26.7% for PTK. Subjects treated with ASP and PTK had failed prior treatment efforts. Conclusions include that RES was commonly associated with trauma and the female gender, and that one-third of conservatively treated episodes and one-quarter of surgically treated episodes (ASP or PTK) recurred.

Advances in cataract surgery and intraocular lenses.

Cataract surgery is one of the most common medical procedures among persons age 65 and older. Once an inpatient procedure, it has become a simple outpatient surgery with extremely low rates of morbidity. With the development of implantable intraocular lenses (IOLs), patients undergoing cataract surgery gained the benefit of corrected pre-existing refractive error, astigmatism, and presbyopia. This article reviews developments in cataract surgery and describes current IOL technology.

Keratoconus in the Medicare population.

PURPOSE: To investigate the population-based prevalence of keratoconus in US individuals aged 65 years and older. DESIGN: Multiyear retrospective cross-sectional claims analysis. METHODS: Fee-for-service claims from a 5% national sample of Medicare beneficiaries aged 65 years and older were reviewed. Claims records were queried on an annual basis for the years 1999 through 2003 for ICD-9 codes specific to keratoconus. The number of beneficiaries with keratoconus-related claims was counted for each calendar year. RESULTS: The number of beneficiaries receiving care for keratoconus rose steadily from 15.7/100,000 beneficiaries in 1999 to 18.5/100,000 in 2003, averaging 17.5/100,000 across the 5 years of the study. Keratoconus rates declined with increasing age but did not differ by gender. Keratoconus care was more prevalent in whites than in other races. CONCLUSIONS: Keratoconus is an uncommon disease in the Medicare population. Longitudinal analysis of Medicare claims data may provide a useful tool for monitoring uncommon diseases, such as keratoconus, in the elderly.

Short-term aerobic exercise training in obese humans with type 2 diabetes mellitus improves whole-body insulin sensitivity through gains in peripheral, not hepatic insulin sensitivity.

CONTEXT: Short-term aerobic exercise training can improve whole-body insulin sensitivity in humans with type 2 diabetes mellitus; however, the contributions of peripheral and hepatic tissues to these improvements are not known. OBJECTIVE: Our objective was to determine the effect of 7-d aerobic exercise training on peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic clamp conditions. DESIGN: Subjects were randomly assigned to one of two groups. The energy balance group consumed an isocaloric diet consisting of 50% carbohydrate, 30% fat, and 20% protein for 15 d. The energy balance plus exercise group consumed a similar diet over the 15 d and performed 50-min of treadmill walking at 70% of maximum oxygen consumption maximum during the second 7 d of the 15-d study period. Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after 1-wk dietary control and a second clamp after completing the study. SETTING: The study was performed at Ohio State University's General Clinical Research Center. PARTICIPANTS: There were 18 obese, mildly diabetic humans included in the study. INTERVENTION: Aerobic exercise training was performed for 7 d. MAIN OUTCOME MEASURES: Whole-body, peripheral, and hepatic insulin sensitivity were measured. RESULTS: Exercise training did not have an impact on peripheral glucose uptake or endogenous glucose production during the basal state or low-dose insulin. Likewise, it did not alter endogenous glucose production during high-dose insulin. However, 1-wk of exercise training increased both whole-body (P<0.05) and peripheral insulin sensitivity (P<0.0001) during high-dose insulin. CONCLUSION: Improvements to whole body insulin sensitivity after short-term aerobic exercise training are due to gains in peripheral, not heptic insulin sensitivity.

Importance of aerobic fitness in cardiovascular risks in sedentary overweight and obese African-American women.

BACKGROUND: Whether the level of aerobic fitness significantly impacts cardiovascular disease (CVD) risks in healthy, nondiabetic, overweight or obese African-American women remains uncertain. OBJECTIVE: To examine the clinical and metabolic risk factors of CVD in nondiabetic, sedentary overweight or obese African-American women with varying degrees of aerobic fitness. METHODS: Forty-eight African-American women, with mean age of 43 +/- 4.2 years and body mass index of 32.3 +/- 3.6 kg/m2, participated in the study. Fasting and 2-hr postprandial serum glucose, insulin, and C-peptide levels were obtained during oral glucose tolerance test. Insulin sensitivity was calculated by Homeostasis Model Assessment (HOMA-IR). Aerobic fitness was categorized empirically as very low aerobic fitness (VLAF; n = 17, VO2max < 21 ml/kg/min), low aerobic fitness (LAF; n = 12, between 21 and 24.4 ml/kg/min), and moderate aerobic fitness (MAF; n = 19, >24.4 ml/kg/min). RESULTS: Significant differences were found in serum glucose, insulin, and C-peptide levels, and HOMA-IR in the VLAF vs. LAF and MAF groups. Mean HOMA-IR was statistically greater in the VLAF and LAF when compared to MAF. Mean fasting serum cholesterol, triglycerides, and low-density lipoprotein cholesterol levels were higher in the VLAF group compared to the MAF group, whereas high-density lipoprotein cholesterol was lower in the VLAF group. Despite differences in the obesity indices and insulin resistance in the three groups, the atherogenic lipids and lipoproteins were within normal limits, irrespective of degree of VO2max. DISCUSSION: Modest aerobic fitness has significant impact on insulin sensitivity and atherogenic lipids and lipoprotein parameters and the overall risks for CVD in sedentary overweight or obese African-American women. Whether modest physical fitness translates into prevention of type 2 diabetes and CVD in African-American women remains to be determined.