The incidence of construction site injuries to women in Delhi: capture-recapture study.

BACKGROUND: In India, the construction sector provides the main alternative to agricultural work - seasonal migration to and from construction work is widespread and construction work remains the second-largest employer of women in the country behind agriculture. Occupational injuries, which kill over 300,000 people annually, are a serious public health concern. However, data on construction site injuries to women are lacking, as India does not publish statistics on occupational injuries and illnesses. Our objectives were to: Estimate the number of women injured in construction site accidents in Delhi; and to estimate and compare the annual construction site injury rates per 100,000 workers of males and females in Delhi. METHODS: We conducted a two-sample capture-recapture study using data for accidents reported to the Delhi Police, Employee State Insurance Corporation (ESIC), and Commissioners of Workmen Compensation (CWC) of Delhi Government. The capture-recapture method has been used in epidemiology, to estimate morbidity and mortality using multiple, overlapping, but incomplete data sources. This study is based on the injuries reported from construction site accidents in Delhi in 2017. We linked the data from each of the data sources using the name, gender, and age of each injured person, the date and place of the accident, and the name of the employer. We used the Chapman estimator to estimate the total incidence of construction injuries in Delhi. RESULTS: We estimated that there was a total of 37 female construction site workers injured (17 fatal and 20 non-fatal) in Delhi in 2017. There was a total of 1043 male construction site workers injured (236 fatal and 807 non-fatal). FIRs ascertained two-thirds (68%) of all injuries to females but only one third (34%) of those to males. The annual construction site injury rate per 100,000 workers of females was 82.26 (95%CI: 57.92 to 113.39). The annual construction site injury rate per 100,000 workers of males was 146.5 (95%CI: 137.7 to 155.6). There was strong evidence (p = 0.001) that the overall construction site injury rate per 100,000 workers of females was about one half the rate of males [rate ratio 0.56 (95%CI: 0.40 to 0.78)]. There was no evidence (p = 0.601) that the rates of fatal injuries differed in males and females (rate ratio 1.14 (95%CI: 0.70 to 1.87). CONCLUSIONS: This study is the first to estimate the incidence of injuries to female construction site workers in India. The overall injury rate of female construction workers was over half as great as the rate of males. This implies that female construction workers face a not insignificant risk. Hence, safety measures (e.g., personal protective equipment) that are appropriate and culturally acceptable to Indian women are needed.

Structure Annotation of All Mass Spectra in Untargeted Metabolomics.

Urine metabolites are used in many clinical and biomedical studies but usually only for a few classic compounds. Metabolomics detects vastly more metabolic signals that may be used to precisely define the health status of individuals. However, many compounds remain unidentified, hampering biochemical conclusions. Here, we annotate all metabolites detected by two untargeted metabolomic assays, hydrophilic interaction chromatography (HILIC)-Q Exactive HF mass spectrometry and charged surface hybrid (CSH)-Q Exactive HF mass spectrometry. Over 9,000 unique metabolite signals were detected, of which 42% triggered MS/MS fragmentations in data-dependent mode. On the highest Metabolomics Standards Initiative (MSI) confidence level 1, we identified 175 compounds using authentic standards with precursor mass, retention time, and MS/MS matching. An additional 578 compounds were annotated by precursor accurate mass and MS/MS matching alone, MSI level 2, including a novel library specifically geared at acylcarnitines (CarniBlast). The rest of the metabolome is usually left unannotated. To fill this gap, we used the in silico fragmentation tool CSI:FingerID and the new NIST hybrid search to annotate all further compounds (MSI level 3). Testing the top-ranked metabolites in CSI:Finger ID annotations yielded 40% accuracy when applied to the MSI level 1 identified compounds. We classified all MSI level 3 annotations by the NIST hybrid search using the ClassyFire ontology into 21 superclasses that were further distinguished into 184 chemical classes. ClassyFire annotations showed that the previously unannotated urine metabolome consists of 28% derivatives of organic acids, 16% heterocyclics, and 16% lipids as major classes.

Identification of small molecules using accurate mass MS/MS search.

Tandem mass spectral library search (MS/MS) is the fastest way to correctly annotate MS/MS spectra from screening small molecules in fields such as environmental analysis, drug screening, lipid analysis, and metabolomics. The confidence in MS/MS-based annotation of chemical structures is impacted by instrumental settings and requirements, data acquisition modes including data-dependent and data-independent methods, library scoring algorithms, as well as post-curation steps. We critically discuss parameters that influence search results, such as mass accuracy, precursor ion isolation width, intensity thresholds, centroiding algorithms, and acquisition speed. A range of publicly and commercially available MS/MS databases such as NIST, MassBank, MoNA, LipidBlast, Wiley MSforID, and METLIN are surveyed. In addition, software tools including NIST MS Search, MS-DIAL, Mass Frontier, SmileMS, Mass++, and XCMS2 to perform fast MS/MS search are discussed. MS/MS scoring algorithms and challenges during compound annotation are reviewed. Advanced methods such as the in silico generation of tandem mass spectra using quantum chemistry and machine learning methods are covered. Community efforts for curation and sharing of tandem mass spectra that will allow for faster distribution of scientific discoveries are discussed.

Increasing Compound Identification Rates in Untargeted Lipidomics Research with Liquid Chromatography Drift Time-Ion Mobility Mass Spectrometry.

Unknown metabolites represent a bottleneck in untargeted metabolomics research. Ion mobility-mass spectrometry (IM-MS) facilitates lipid identification because it yields collision cross section (CCS) information that is independent from mass or lipophilicity. To date, only a few CCS values are publicly available for complex lipids such as phosphatidylcholines, sphingomyelins, or triacylglycerides. This scarcity of data limits the use of CCS values as an identification parameter that is orthogonal to mass, MS/MS, or retention time. A combination of lipid descriptors was used to train five different machine learning algorithms for automatic lipid annotations, combining accurate mass ( m/ z), retention time (RT), CCS values, carbon number, and unsaturation level. Using a training data set of 429 true positive lipid annotations from four lipid classes, 92.7% correct annotations overall were achieved using internal cross-validation. The trained prediction model was applied to an unknown milk lipidomics data set and allowed for class 3 level annotations of most features detected in this application set according to Metabolomics Standards Initiative (MSI) reporting guidelines.

The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study.

The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score ≥ 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. INTRODUCTION: This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. METHODS: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. RESULTS: The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score ≥ 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. CONCLUSIONS: The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.

Frequency of discontinuation of injectable osteoporosis therapies in US patients over 2 years.

Little is known about treatment patterns with injectable osteoporosis therapies. At 12 months, the probability of discontinuation was 69.1% among patients using ibandronate, followed by teriparatide (67.1%), zoledronic acid (59.2%), and denosumab (48.8%). By 24 months, discontinuation was higher for each treatment. The majority of US patients discontinue injectable osteoporosis treatment by the end of the first year following initiation. INTRODUCTION: This study was designed to assess the frequency of treatment discontinuation over time among patients who initiate injectable osteoporosis therapies. METHODS: This retrospective observational study utilized an administrative claims database to measure discontinuation of injectable osteoporosis therapy, reported at 6-month intervals over 2 years. Eligible patients were aged ≥55 years, had newly initiated injectable osteoporosis therapy between January 2008 and June 2012, and were continuously enrolled in the health plan for ≥1 year prior to and ≥1.5 years after the date the first injectable medication was received (the index date). Follow-up time ranged from 18 to 24 months. Injectable osteoporosis treatments included in the analysis were denosumab, ibandronate, teriparatide, and zoledronic acid. Discontinuation was assessed using Kaplan-Meier survival analysis and was defined at each time point as the percentage of patients who did not receive the dose scheduled for that time point. A 90-day grace period was allowed to accommodate flexibility in the scheduling of post-index re-administrations. Sensitivity analyses assessed discontinuation using grace periods of 60 and 30 days. RESULTS: A total of 4756 patients met the inclusion criteria for the study, with 617 utilizing denosumab, 233 ibandronate, 778 teriparatide, and 3128 zoledronic acid. At 12 months, discontinuation was highest among patients using ibandronate (69.1%), followed by teriparatide (67.1%), zoledronic acid (59.2%), and denosumab (48.8%). By 24 months, discontinuation was higher for each treatment: 87.5% for ibandronate, 87.9% for teriparatide, 79.8% for zoledronic acid, and 64.3% for denosumab. CONCLUSIONS: The majority of US patients discontinue injectable osteoporosis treatment by the end of the first year following initiation.

Association of gastrointestinal events with quality of life and treatment satisfaction in osteoporosis patients: results from the Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS).

The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. INTRODUCTION: The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. METHODS: MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. RESULTS: Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (-0.04 for the EQ-5D utility score, -5.07 for the EQ-5D visual analog scale, -3.35 for OPAQ physical function, -4.60 for OPAQ emotional status, and -8.50 for OPAQ back pain; P ≤ 0.001 for all values). Decrements in month 12 treatment satisfaction scores were -6.46 for patients with baseline GI events and -7.88 for patients with post-baseline GI events. CONCLUSIONS: The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis.

Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study.

SUMMARY: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. INTRODUCTION: The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. METHODS: Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0-22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0-100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0-1; OPAQ-SV, score 0-100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. RESULTS: A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1% of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, -0.43; OPSAT-Q, -5.68; EQ-5D, -0.04 (new users) and -0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, -4.17 (experienced users); emotional status, -4.28 (new users) and -5.68 (experienced users); back pain, -5.82 (new users) and -11.33 (experienced users), all P < 0.01. CONCLUSIONS: Patients with GI symptoms have lower treatment adherence and treatment satisfaction and worse HRQoL than patients without GI symptoms.

Post-fracture pharmacotherapy for women with osteoporotic fracture: analysis of a managed care population in the USA.

UNLABELLED: Pharmacologic therapy is recommended to reduce future fracture risk. We examined osteoporosis medications dispensed to older women after first fracture. Only 23 % received therapy during the first year post-fracture. Prior osteoporosis therapy, a prior osteoporosis diagnosis, and older age were good predictors of post-fracture osteoporosis therapy. INTRODUCTION: Pharmacologic therapy is recommended after osteoporotic fracture to reduce future fracture risk. The objective of this retrospective study was to examine osteoporosis therapy dispensed to women post-fracture. METHODS: We identified women ≥50 years old in a large administrative claims database from 2003 to mid-2012 who were continuously enrolled 2 years before (baseline) and 1 year after first osteoporotic fracture. Exclusions were Paget's disease or malignant neoplasm. Pre- and post-fracture osteoporosis therapies (oral and parenteral) were assessed overall and by fracture site. RESULTS: A total of 47,171 women of mean (SD) age of 63 (10) years were eligible; fractures included 8 % hip, 17 % vertebral, 73 % non-hip/non-vertebral, and 3 % multiple fracture sites. Only 18 % received osteoporosis therapy within 90 days and 23 % within 1 year post-fracture. Overall, 19 % of women had a prior osteoporosis diagnosis; 20 % had received osteoporosis therapy during baseline. Of 37,649 (80 %) women without baseline therapy, only 9 % initiated pharmacologic therapy within 1 year. The adjusted odds ratio (OR) of therapy within 1 year post-fracture was significantly greater for women who had received baseline osteoporosis therapy (versus none) and who had vertebral (OR 12.7, 95 % confidence interval (CI) 11.2-14.5), hip (15.2, 12.5-18.7), or non-hip/non-vertebral fracture (34.4, 31.7-37.3). Other significant predictors included pre-fracture osteoporosis diagnosis (1.6, 1.4-1.7) and older age (OR range, 1.3-1.7). Treatment adherence was significantly better among women with baseline osteoporosis diagnosis. CONCLUSIONS: The substantial post-fracture treatment gap represents an important unmet need for women with osteoporotic fractures. Fracture liaison or adherence programs could lead to improved post-fracture treatment rates.

Indole-3-acetic acid biosynthetic pathway and aromatic amino acid aminotransferase activities in Pantoea dispersa strain GPK.

This investigation deals with the production of IAA by a bacterial isolate Pantoea dispersa strain GPK (PDG) identified by 16S rRNA gene sequence analysis. HPLC and Mass spectral analysis of metabolites from bacterial spent medium revealed that, IAA production by PDG is Trp-dependent and follows indole-3-pyruvic acid (IPyA) pathway. Substrate specificity study of aromatic amino acid aminotransferase (AAT) showed high activities, only when tryptophan (Trp) and α-ketoglutarate (α-kg) were used as substrates. AAT is highly specific for Trp and α-kg as amino group donor and acceptor, respectively. The effect of exogenous IAA on bacterial growth was established. Low concentration of exogenous IAA induced the growth, whereas high concentration decreased the growth of bacterium. PDG treatment significantly increased the root length, shoot length and dry mass of the chickpea and pigeon pea plants.

Rib fracture as a predictor of future fractures in young and older postmenopausal women: National Osteoporosis Risk Assessment (NORA).

UNLABELLED: A rib fracture history after age 45 was associated with a 5.4-fold increase in new rib fracture risk and a 2.4-fold increase in risk of any new clinical fracture in 155,031 postmenopausal women. A rib fracture history suggests osteoporosis and should be considered when evaluating patients for interventions to prevent fractures. INTRODUCTION: Until recently, little attention was paid to rib fracture as an osteoporosis marker. Emerging evidence suggests rib fracture may be an osteoporotic fracture in men and women. We report the 5-year independent association between baseline rib fracture histories and self-reported future fractures by age (decade) in the NORA cohort (155,031 postmenopausal women, 50-99 years). METHODS: Participants reported fracture history and responded to follow-up surveys at years 1, 3, or 6. Women with a baseline rib fracture history without other fractures were compared with women with no fracture. RESULTS: At baseline, 4,758 (3.07%) women reported a rib fracture history without other fractures; 6,300 women reported 6,830 new clinical fractures, including wrist (2,271), rib (1,891), spine (1,136), hip (941), and forearm (591). Adjusted relative risk (ARR) values (95% confidence interval [CI]) for future fractures in women with rib fracture history versus women with no fracture history were 5.4 (4.8-6.1) at the rib, 2.1 (1.7-2.6) at the spine, and 1.4 (1.1-1.7) at the wrist, and not significant for forearm or hip fractures. Future fracture risk was at least doubled in women with a rib fracture history in all ages: ARR (95% CI) 3.4 (2.8-4.0) for ages 50-59, 2.5 (2.1-3.0) for ages 60-69, 2.0 (1.7-2.3) for ages 70-79, and 2.0 (1.6-2.6) for ages >80. CONCLUSIONS: Rib fracture, the second most common clinical fracture in women (after wrist fracture), predicted future fractures of the rib, wrist, and spine at all ages. Women presenting with rib fractures should be evaluated for appropriate management to prevent future fractures.

Completeness of Ascertainment of Construction Site Injuries Using First Information Reports (FIRs) of Indian Police: Capture-Recapture Study.

BACKGROUND & OBJECTIVES: The construction industry is a leading contributor to occupational injuries. First Information Reports (FIRs) of Indian Police are a potential data source for construction injuries. The aim of this study was to estimate the completeness of ascertainment of construction site injuries by FIRs. METHODS: This was a two-sample capture-recapture study of construction site injuries sustained in the year 2017 in Delhi, India. The first capture sample was data extracted from FIRs. The second capture sample comprised data extracted from the Employee State Insurance Corporation (ESIC) and the Commissioners of Workmen Compensation. The Chapman estimator was used to estimate, with 95% confidence intervals, the total numbers of fatal and non-fatal injuries. RESULTS: FIRs ascertained 374 injuries (110 fatal and 264 non-fatal) while the combined data of ESIC and workmen compensation claims ascertained 80 injuries (48 fatal and 32 non-fatal). The capture-recapture analysis estimated that 1,011 (95% CI: 873 to 1149) injuries: 258 (95% CI: 221 to 295) fatal injuries and 873 (95% CI: 765 to 1053) non-fatal injuries were sustained in Delhi in 2017. INTERPRETATION & CONCLUSIONS: FIRs ascertain approximately one-third of all construction site injuries. In the absence of any other data source, FIRs may be used as the basis of a construction injury surveillance system, recognizing that any estimates made using these data must be adjusted to allow for the approximately two-thirds of injuries not reported to the police. Further research is needed to identify reasons for some injuries not being reported to the police, in order to help to develop a strategy to improve the completeness of ascertainment of construction site injuries for the future.

How Safe Are Industries in India? Ascertaining Industrial Injuries in Dadra and Nagar Haveli, India by Capture-Recapture Method.

CONTEXT: Every year, more than 4 million people die from injuries worldwide. India reported 413,457 deaths due to unintentional injuries in 2015. Manufacturing industry is a major contributor to injury morbidity and mortality. AIMS: This study aims to estimate the burden of industrial injuries in Dadra and Nagar Haveli, India. SETTINGS AND DESIGN: Dadra and Nagar Haveli is a small territory spread over 491 sq. km, having a population of 343,709 as per 2011 population census. METHODS AND MATERIALS: The two-sample capture-recapture method was used for ascertainment of fatal and non-fatal injuries reported from 1st January to 31st December 2017. The first capture was data of injuries extracted from First Information Reports registered by the police. The recapture was data of injuries reported by the government health facilities. STATISTICAL ANALYSIS USED: Chapman estimator was used to derive total fatal and non-fatal injuries. An analysis was done using Microsoft Excel software. RESULTS: According to police records, there were nine fatal and eight non-fatal injuries during the study period. Health facilities reported 21 fatal and 113 non-fatal injuries. Six cases of fatal and 3 cases of non-fatal injuries were found in both the data sources. The capture-recapture analysis estimated 30 fatal (95% CI: 20 to 40) and 225 non-fatal injuries (95% CI: 90 to 420). CONCLUSIONS: Both records of police and government health facilities underestimate fatal and non-fatal injuries with under-reporting more pronounced in police records.

A type IV secretion system contributes to intracellular survival and replication of Burkholderia cenocepacia.

Burkholderia cenocepacia is an important respiratory pathogen in persons with cystic fibrosis (CF). Recent studies indicate that B. cenocepacia survives within macrophages and airway epithelial cells in vitro by evading endosome-lysosome fusion. We investigated the role of a plasmid-encoded type IV secretion system in the intracellular survival, replication, and processing of B. cenocepacia. Both a wild-type strain (K56-2) and its type IV secretion system mutant (designated LC101) entered and replicated in CF airway epithelial cells and monocyte-derived macrophages. However, significantly more intracellular K56-2 than LC101 bacteria were found in both cell types at 24 h postinfection. Colocalization of bacteria with markers of the classical endocytic pathway indicated that although both K56-2 and LC101 reside transiently in early endosomes, a greater proportion of the mutant bacteria are targeted to lysosomal degradation. In contrast, wild-type bacteria escape from the classical endocytic pathway and traffic to the endoplasmic reticulum, where they replicate. Our results show that the intracellular processing of B. cenocepacia is similar in both professional and nonprofessional phagocytes and that a functional plasmid-encoded type IV secretion system contributes to the survival and replication of B. cenocepacia in eukaryotic cells.

Impact of gastrointestinal events on patient-reported outcomes in Asia-Pacific women with osteoporosis: baseline results of the MUSIC OS-AP study.

The purpose of this study was to describe the impact of gastrointestinal events on patient-reported outcomes and health care resource use among Asia-Pacific women with postmenopausal osteoporosis. The results of this study show that gastrointestinal events decreased adherence, treatment satisfaction, and quality of life in Asia-Pacific women with postmenopausal osteoporosis. PURPOSE: This study aimed to describe the impact of gastrointestinal (GI) events on patient-reported outcomes and health care resource use among Asia-Pacific women with postmenopausal osteoporosis. METHODS: The MUSIC OS-AP study included an observational cohort study of postmenopausal women with osteoporosis. Women were classified as untreated or treated, with treated patients further classified as new or experienced users. Adherence was measured by the Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire, treatment satisfaction by the Osteoporosis Patient Satisfaction Questionnaire (OPSAT) while general health-related and osteoporosis-specific quality of life were measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire and the Osteoporosis Assessment Questionnaire (OPAQ), respectively. The association of GI events with these outcomes was determined by covariate-adjusted regression analysis of least squares mean differences in the scores of treated patients with and without GI events. Resource utilization was measured as the number of physician visits over the past 3 months, and multivariate regression analysis was used to assess the association of GI events with the likelihood of a visit. RESULTS: The GI event profile, quality of life scores, and resource use were numerically similar in untreated and treated women. The rate of adherence among treated women was higher in experienced than in new users. As indicated by mean scores, experienced users had better quality of life and slightly higher treatment satisfaction and fewer physician visits than new users. Except for adherence in new users, all measures were similarly adversely affected by GI events in both new and experienced users. CONCLUSIONS: GI events decreased adherence, treatment satisfaction, and quality of life in Asia-Pacific women with postmenopausal osteoporosis.

Influence of gastrointestinal events on treatment of osteoporosis in Asia-Pacific women: Perspectives from physicians in the MUSIC OS-AP study.

BACKGROUND: The objectives of the physician survey component of the MUSIC OS-AP study were to describe physicians' approaches to treatment of women with postmenopausal osteoporosis and to understand the influence of gastrointestinal (GI) events on treatment in clinical practice. METHODS: Physicians were recruited from 5 Asia-Pacific countries. Questionnaires collected information about physicians' standard practices for treatment of patients with osteoporosis, as well as their perspectives on the influence of GI events on osteoporosis treatment approaches. RESULTS: A total of 59 physicians participated in the study. The most frequently prescribed or recommended treatments were vitamin D (84% of patients), calcium (82%), and oral bisphosphonates (59%). When choosing a medication for treatment-naïve patients, GI sensitivity was often or always a factor for 79% of physicians. Among physicians not prescribing pharmacologic treatment, a mean of 18% of non-prescriptions were due to GI sensitivity. For patients with pre-existing GI conditions, physicians most frequently ranked use of non-oral osteoporosis medication as the first treatment strategy (47%), followed by co-prescription with a proton pump inhibitor or other gastro-protective agent (31%). For patients developing GI symptoms after starting pharmacologic treatment, the most frequently first-ranked management strategy was to check if patients were taking their osteoporosis medication correctly as prescribed (64%), followed by temporary discontinuation of the medication (i.e., a drug holiday) until GI events have resolved (31%) and co-prescription with a proton pump inhibitor or other gastroprotective agent (24%). CONCLUSIONS: These results suggest that GI events influence the prescribing practices of physicians in the Asia-Pacific region and sometimes result in non-treatment of women with osteoporosis.

Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.

In mass spectrometry-based untargeted metabolomics, rarely more than 30% of the compounds are identified. Without the true identity of these molecules it is impossible to draw conclusions about the biological mechanisms, pathway relationships and provenance of compounds. The only way at present to address this discrepancy is to use in silico fragmentation software to identify unknown compounds by comparing and ranking theoretical MS/MS fragmentations from target structures to experimental tandem mass spectra (MS/MS). We compared the performance of four publicly available in silico fragmentation algorithms (MetFragCL, CFM-ID, MAGMa+ and MS-FINDER) that participated in the 2016 CASMI challenge. We found that optimizing the use of metadata, weighting factors and the manner of combining different tools eventually defined the ultimate outcomes of each method. We comprehensively analysed how outcomes of different tools could be combined and reached a final success rate of 93% for the training data, and 87% for the challenge data, using a combination of MAGMa+, CFM-ID and compound importance information along with MS/MS matching. Matching MS/MS spectra against the MS/MS libraries without using any in silico tool yielded 60% correct hits, showing that the use of in silico methods is still important.

Mechanism of lectin-cell interactions: thermodynamic and kinetic analysis of the binding of winged bean acidic lectin (WBA II) to human erythrocytes.

In order to identify the forces involved in the binding and to understand the mechanism involved, equilibrium and kinetic studies were performed on the binding of the winged bean acidic lectin to human erythrocytes. The magnitudes of delta S and delta H were positive and negative respectively, an observation differing markedly from the lectin-simple sugar interactions where delta S and delta H are generally negative. Analysis of the sign and magnitudes of these values indicate that ionic and hydrogen bonded interactions prevail over hydrophobic interactions resulting in net -ve delta H (-37.12 kJ.mol-1) and +ve delta S (14.4 J.mole-1 K-1 at 20 degrees C), thereby suggesting that this entropy driven reaction also reflects conformational changes in the lectin and/or the receptor. Presence of two kinds of receptors for WBA II on erythrocytes, as observed by equilibrium studies, is consistent with the biexponential dissociation rate constants (at 20 degrees C K1 = 1.67 x 10(-3) M-1 sec-1 and K2 = 11.1 x 10(-3) M-1 sec-1). These two rate constants differed by an order of magnitude accounting for the difference in the association constants of the two receptors of WBA II. However, the association process remains monoexponential suggesting no observable difference in the association rates of the lectin molecule with both the receptors, under the experimental conditions studied. The thermodynamic parameters calculated from kinetic data correlate well with those observed by equilibrium. A two-step binding mechanism is proposed based on the kinetic parameters for WBA II-receptor interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of amino groups in the carbohydrate binding activity of winged bean acidic agglutinin.

Chemical modification studies reveal that the modification of amino groups in WBA II leads to a complete loss in the hemagglutinating and saccharide binding activities. Since WBA II is a dimeric molecule and contains two binding sites, one amino group in each of the binding sites is inferred to be essential for its activity. The presence of amino group which has a potential to form hydrogen bonded interactions with the ligand, substantiates our observation regarding the forces involved in WBA II-receptor and WBA II-simple sugar interactions.

Up-regulation of matrix metallopeptidase 12 in motor neurons undergoing synaptic stripping.

Axotomy of the rodent facial nerve represents a well-established model of synaptic plasticity. Post-traumatic "synaptic stripping" was originally discovered in this system. We report upregulation of matrix metalloproteinase MMP12 in regenerating motor neurons of the mouse and rat facial nucleus. Matrix metalloproteinases (matrix metallopeptidases, MMPs) are zinc-binding proteases capable of degrading components of the extracellular matrix and of regulating extracellular signaling networks including within synapses. MMP12 protein expression in facial motor neurons was enhanced following axotomy and peaked at day 3 after the operation. The peak of neuronal MMP12 expression preceded the peak of experimentally induced synaptic plasticity. At the same time, MMP12 redistributed intracellularly and became predominantly localized beneath the neuronal somatic cytoplasmic membrane. Both findings point to a role of MMP12 in the neuronal initiation of the synaptic stripping process. MMP12 is the first candidate molecule for such a trigger function and has potential as a therapeutic target. Moreover, since statins have been shown to increase the expression of MMP12, interference with synaptic stability may represent one mechanism by which these widely used drugs exert their side effects on higher CNS functions.