Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials.

AIMS: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. MATERIALS AND METHODS: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4). RESULTS: Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2. CONCLUSIONS: Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning.

A comparative analysis between next-generation sequencing and conventional culture method to detect empyema-associated microorganisms: A systematic review.

Empyema poses a significant global health concern, yet identifying responsible bacteria remains elusive. Recent studies question the efficacy of conventional pleural fluid culture in accurately identifying empyema-causing bacteria. The aim of this study was to compare diagnostic capabilities of next-generation sequencing (NGS) with conventional pleural fluid culture in identifying empyema-causing bacteria. Five databases (Google Scholar, Science Direct, Cochrane, Research Gate, and PubMed) were used to search studies comparing conventional pleural fluid culture with NGS for identifying empyema-causing bacteria using keywords. Positive results identified through conventional pleural fluid culture and NGS were extracted. In addition, bacterial profiles identified by NGS were also documented. Joanna-Briggs Institute (JBI) critical appraisal tool was employed to assess quality of included studies. Descriptive analysis was employed to present outcome of interests. From five databases, three studies, with 354 patients, were included. Findings from three studies showed that NGS outperformed conventional pleural fluid culture in detecting empyema-causing bacteria even in culture-negative samples. Moreover, dominant bacterial profiles identified through NGS included Streptococcus pneumoniae, Staphylococcus aureus, and anaerobic bacteria. In conclusion, NGS outperforms conventional pleural fluid culture in detection empyema-causing bacteria, yet further studies with larger samples and broader bacterial profiles are needed to increase confidence and urgency in its adoption over conventional pleural fluid culture.

Gastric cancer with enhanced myogenesis is associated with less cell proliferation, enriched epithelial-to-mesenchymal transition and angiogenesis, and poor clinical outcomes.

Gastric cancer (GC) remains a lethal disease, with over 26,000 new cases and more than 11,000 deaths annually in the US. Thus, a deeper understanding of GC biology is critical to improve survival. Myogenesis is the formation of muscle fibers, which is a mesodermal tissue. In cancer, epithelial-to-mesenchymal transition (EMT) is a known phenomenon that promotes metastasis and poor survival. Given that myogenesis produces mesenchymal cells, we hypothesized that GC with increased myogenesis is linked to aggressive tumor behaviors and less favorable outcomes. In this study, three GC patient cohorts: TCGA (n=375), GSE26253 (n=432), and GSE84437 (n=482), were analyzed. The "MYOGENESIS" set in the Hallmark collection which comprises 200 myogenesis-related genes was analyzed to perform gene set variation analysis to create a score to quantify the myogenesis activity. Our results showed that T category of AJCC cancer staging that reflects the tumor invasion to stomach wall consistently correlated with myogenesis activity in two GC cohorts. High myogenesis GC was associated with lower cell proliferation, evidenced by reduced proliferation scores, decreased Ki67 gene expression, and less enrichment of E2F Targets, G2M checkpoint, MYC Targets V1, and V2 gene sets. High myogenesis tumors showed increased stromal cells (fibroblasts and adipocytes) infiltration within the tumor microenvironment, as well as less silent and non-silent mutation rates and copy number alterations. Higher lymphocyte infiltration, leukocyte fraction, T-cell receptor richness, and B-cell receptor richness were associated with high myogenesis GC. However, infiltration of CD4 cells, T helper type 1 and 2 cells, Natural Killer cells, regulatory T cells, and plasma cells was lower, with increased infiltration of dendritic cells in high myogenesis GC. High myogenesis GC enriched EMT, Hedgehog, TGF-ß, and KRAS gene sets. Furthermore, it was associated with enhanced angiogenesis, evidenced by enrichment of Angiogenesis, Coagulation, and Hypoxia gene sets, and increased infiltration of microvascular and lymphatic endothelial cells and pericytes. High myogenesis GC consistently correlated with worse overall survival in all three cohorts, and worse disease-specific and progression-free survival in the TCGA cohort. Hence, our findings suggest that GC with enhanced myogenesis is associated with decreased cell proliferation, increased EMT and angiogenesis, and worse prognosis.

Review of an international pilot project to adapt the Canadian Adult Obesity Clinical Practice Guideline.

Background: The evidence-based Canadian Adult Obesity Clinical Practice Guideline (CPG) released in August 2020 were developed through a systematic literature review and patient-oriented research process. This CPG is considered a paradigm shift for obesity care as it introduced a new obesity definition that is based on health not body size, incorporates lived experiences of people affected by obesity, and addresses the pervasive weight bias and stigma that patients face in healthcare systems. The purpose of this pilot project was to assess the feasibility of adapting the Canadian CPG in Chile and Ireland. Methods: An International Clinical Practice Guideline Adaptation Committee was established to oversee the project. The project was conducted through four interrelated phases: 1) planning and preparation; 2) pilot project application process; 3) adaptation; and 4) launch, dissemination, and implementation. Ireland used the GRADE-ADAPTE framework and Chile used the GRADE-ADOLOPMENT approach. Results: Chile and Ireland developed their adapted guidelines in one third of the time it took to develop the Canadian guidelines. In Ireland, 18 chapters, which underpin the 80 key recommendations, were contextually adapted. Chile adopted 18 chapters and 76 recommendations, adapted one recommendation, and developed 12 new recommendations.. Conclusion: The pilot project demonstrated it is feasible to adapt the Canadian CPG for use in other countries with different healthcare systems, languages, and cultural contexts, while retaining the Canadian CPG's key principles and values such as the treatment of obesity as a chronic disease, adoption of new clinical assessment approaches that go beyond anthropometric measurements, elimination of weight bias and stigma, shifting obesity care outcomes to improved health and well-being rather than weight loss alone, and the use of patient-centred, collaborative and shared-decision clinical care approaches.

Colitis as the Initial Presentation of Eosinophilic Granulomatosis with Polyangiitis.

A male patient in his early sixties with recurrent diarrhea was transferred to our hospital. The patient did not have any pulmonary or upper respiratory symptoms. He was noted to have peripheral eosinophilia. Further workup revealed a negative antineutrophilic cytoplasmic antibody titer but a positive myeloperoxidase antibody and positive proteinase 3 antibodies. A colon biopsy also revealed eosinophilic-rich granulomas in the mucosa, confirming a diagnosis of eosinophilic granulomatosis with polyangiitis. On cardiac imaging, eosinophilic myocarditis was also discovered. To treat active severe EGPA, the patient received high-dose corticosteroids and intravenous cyclophosphamide. The occurrence of gastrointestinal involvement as an initial manifestation of eosinophilic granulomatosis with polyangiitis is infrequent, emphasizing the significance of its recognition. This case underscores the importance of identifying and diagnosing such atypical presentations to facilitate timely and appropriate management.

Impact of a Powdered Meal Replacement on Metabolism and Gut Microbiota (PREMIUM) in individuals with excessive body weight: a study protocol for a randomised controlled trial.

INTRODUCTION: Excess body weight is associated with a state of low-grade chronic inflammation and alterations of the gut microbiome. Powdered meal replacements (PMR) have been shown to be an effective strategy for weight management; however, their effect on inflammation and the gut microbiome remains unclear. The aim of this 12-week randomised control clinical trial is to investigate the effects of PMR consumption, here given as a soy-yoghurt-honey formula, on inflammation, gut microbiome and overall metabolism in individuals with excessive body weight. METHODS AND ANALYSIS: Healthy adults with excess body weight (n=88) are being recruited and randomly assigned to one of the following groups: (1) Control group (CON): maintaining usual diet for 12 weeks, or (2) PMR group: replacing morning and afternoon snacks daily with a PMR for 12 weeks. Participants are asked to maintain body weight throughout the study and fill out a journal with information about PMR consumption, body weight, food intake, appetite sensations and medications. Three study visits are required: baseline, week 6 and week 12. Outcome measures include systemic inflammatory biomarkers, gut microbiome composition, metabolic blood markers, host energy metabolism, body composition, appetite sensations and host gene expression profile. ETHICS AND DISSEMINATION: This research protocol was approved by the University of Alberta Ethics Board (Pro00070712) and adheres to the Canadian Tri-Council Policy statement on the use of human participants in research. Procedures and potential risks are fully discussed with participants. Study findings will be disseminated in peer-reviewed journals, conference presentations and social media. TRIAL REGISTRATION NUMBER: NCT03235804.

Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.

Parents as Agents of Change in Managing Pediatric Obesity: A Randomized Controlled Trial Comparing Cognitive Behavioral Therapy versus Psychoeducation Interventions.

Background: Obesity interventions for parents of children with obesity can improve children's weight and health. This randomized controlled trial (RCT) evaluated whether a parent-based intervention based on cognitive behavioral therapy (CBT) principles was superior to a parent-based intervention based on a psychoeducation program (PEP) in improving children's obesity. Methods: This study was a pragmatic, two-armed, parallel, superiority RCT. Conducted at a Canadian outpatient pediatric obesity management clinic (September 2010-January 2014), this trial included families with children 8-12 years with an age- and sex-specific BMI ≥85th percentile. The 16-week manualized interventions were similar in content and delivered to parents exclusively, with different theoretical underpinnings. The primary outcome was children's BMI z-score at postintervention (4 months). Secondary outcomes included anthropometric, lifestyle, psychosocial, and cardiometabolic variables. Data were collected at preintervention (0 months), postintervention (4 months), 10, and 16 months. Intention-to-treat analysis using linear mixed models was used to assess outcomes. Results: Among 52 randomly assigned children, the mean age (standard deviation) was 9.8 (1.7) years and BMI z-score was 2.2 (0.3). Mean differences in BMI z-score were not significantly different between the CBT (n = 27) and PEP (n = 25) groups from 0 to 4-, 10-, and 16-month follow-up. At 4 months, the mean difference in BMI z-score from preintervention between the CBT (-0.05, 95% CI = -0.09 to 0.00) and PEP (-0.04, 95% CI = -0.09 to 0.01) groups was -0.01 (95% CI = -0.08 to 0.06, p = 0.80). Similar results were found across all secondary outcomes. Conclusions: Our CBT-based intervention for parents of children with obesity was not superior in reducing BMI z-score vs. our PEP-based intervention.

Efficacy of pretomanid-containing regiments for drug-resistant tuberculosis: A systematic review and meta-analysis of clinical trials.

Concerns regarding the rise of drug-resistant tuberculosis (DR-TB) infections and the need for new drugs with shorter treatment time and fewer side effects have been voiced by the World Health Organization (WHO). The WHO revised its guideline to treat multidrug resistant tuberculosis (MDR-TB) with a 6-month course of BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) in 2022. However, a thorough study and meta-analysis of available evidence is required due to the limited confidence of the evidence confirming the effectiveness of pretomanid-containing regiments. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of pretomanid-containing regiments in treating DR-TB patients. Data from six search engines were searched using inclusion criteria based on the PICOS framework. The keywords of pretomanid and tuberculosis or their alternatives were used. Using RoB2 Cochrane risk-of-bias tool for randomized clinical trials, data were independently extracted and the quality of the data was evaluated. Odds ratio (OR) and heterogeneity tests were used and the findings were presented in ORs and forest plots. A total of four studies with 237 patients was included in the final analysis and 204 (86%) patients had favorable outcome (cured) and 33 (14%) was not cured. Pretomanid-containing regimen (OR: 46.73; 95%CI: 11.76-185.7) and BPaLM/BPaL (OR: 41.67; 95%CI: 8.86-196.73) regimens were associated with favorable outcome (cured). This meta-analysis indicates that the pretomanid-containing regimen and the BPaLM/BPaL regimen could increase the chance to have favorable outcome in DR-TB patients.

Comparative Evaluation of Cotton PTFE Tape and Foam Pellets as Endodontic Spacer in Primary Teeth: An In Vivo Study.

Aim and objective: This study was conducted to microbiologically evaluate cotton, PTFE tape, and foam pellets as endodontic spacer in primary teeth. Materials and methods: Thirty primary second molars indicated for pulpectomy were included in this study. Followed by the completion of pulpectomy in each teeth cotton, PTFE tape, and foam pellets were placed as endodontic spacers randomly in 10 teeth each. The samples were collected from the pulp chamber at baseline and after 7 days to evaluate for microbial contamination of the same. The data obtained was tabulated and subjected to appropriate statistical analysis. Results: There was a statistically significant increase in the colony forming unit after 7 days in cotton and foam pellet group. But PTFE tape group showed very minimal contamination of the pulp chamber after 7 days. Conclusion: Within the limitations of this study, it can be concluded that PTFE tape found to be the best alternative to cotton as an endodontic spacer. Clinical significance: In case of multiple visit pulpectomy procedure, the state of sterility must be maintained in between the appointments until a definitive coronal restoration is placed following root-canal obturation. So it is mandatory to place an endodontic spacer under a provisional restoration to maintain the patency of the root canals and prevention of the microbial growth. The PTFE tape is inorganic, nonfibrous material which can be tightly packed without any voids under the provisional restoration. So PTFE tape is the best material to maintain the root canal patency and to provide a sterile environment by preventing the microbial growth under the provisional restoration as an endodontic spacer material in between the appointments. How to cite this article: Somani R, Arya MV, Singh DJ, et al. Comparative Evaluation of Cotton PTFE Tape and Foam Pellets as Endodontic Spacer in Primary Teeth: An In Vivo Study. Int J Clin Pediatr Dent 2022;15(1):74-78.

Evaluation of physicochemical and biological properties of nonreconstituted MYL-1401O vials, reconstituted MYL-1401O suspension in vial, and diluted MYL-1401O suspension in infusion bags (0.9% saline) for extended duration.

BACKGROUND: MYL-1401O; trastuzumab-dkst (Ogivri™; Mylan Inc.) is a biosimilar to the trastuzumab reference product (Herceptin®; Genentech, USA). Assessment of physicochemical stability and biological activity for the non-reconstituted, reconstituted, and infused solution over an extended, clinically relevant duration is critical for ensuring optimal patient outcomes and health resource utilization. METHODS: The physicochemical and biological stability of MYL-1401O was assessed in non-reconstituted vials stored at 25 °C ± 2 °C/60% ± 5% relative humidity (RH) for 6 months, reconstituted 21 mg/mL solution in vials stored at 2 °C to 8 °C for 10 days, and diluted in 0.9% saline-containing infusion bags at 0.3 mg/mL and 4.0 mg/mL stored for 77 days at 2 °C to 8 °C, plus an additional 2 days at 25 °C ± 2 °C/60% ± 5% RH. RESULTS: At all storage conditions tested, MYL-1401O was physicochemically and biologically stable for extended duration and under various temperature and humidity conditions. CONCLUSIONS: MYL-1401O retained its physicochemical and biological stability under different storage conditions, which supports advanced preparation of MYL-1401O, better efficiency, less wastage, and cost-savings for better patient management.

A high-protein total diet replacement alters the regulation of food intake and energy homeostasis in healthy, normal-weight adults.

PURPOSE: Dietary intake can affect energy homeostasis and influence body weight control. The aim of this study was to compare the impact of high-protein total diet replacement (HP-TDR) versus a control (CON) diet in the regulation of food intake and energy homeostasis in healthy, normal-weight adults. METHODS: In this acute randomized controlled, cross-over study, participants completed two isocaloric arms: a) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat; b) CON: 55% carbohydrate, 15% protein, and 30% fat. The diets were provided for 32 h while inside a whole-body calorimetry unit. Appetite sensations, appetite-related hormones, and energy metabolism were assessed. RESULTS: Forty-three healthy, normal-weight adults (19 females) participated. Appetite sensations did not differ between diets (all p > 0.05). Compared to the CON diet, the change in fasting blood markers during the HP-TDR intervention was smaller for peptide tyrosine-tyrosine (PYY; - 18.9 ± 7.9 pg/mL, p = 0.02) and greater for leptin (1859 ± 652 pg/mL, p = 0.007). Moreover, postprandial levels of glucagon-like peptide 1 (1.62 ± 0.36 pM, p < 0.001) and PYY (31.37 ± 8.05 pg/mL, p < 0.001) were higher in the HP-TDR. Significant correlations were observed between energy balance and satiety (r = - 0.41, p = 0.007), and energy balance and PFC (r = 0.33, p = 0.033) in the HP-TDR. CONCLUSION: Compared to the CON diet, the HP-TDR increased blood levels of anorexigenic hormones. Moreover, females and males responded differently to the intervention in terms of appetite sensations and appetite-related hormones. TRIAL REGISTRATION: NCT02811276 (retrospectively registered on 16 June 2016) and NCT03565510 (retrospectively registered on 11 June 2018).

Using the Edmonton Obesity Staging System in the real world: a feasibility study based on cross-sectional data.

BACKGROUND: The Edmonton Obesity Staging System (EOSS) combined with body mass index (BMI) enables improved functional and prognostic assessment for patients. To facilitate application of the EOSS in practice, we aimed to create tools for capturing comorbidity assessments in electronic medical records and for automating the calculation of a patient's EOSS stage. METHODS: In this feasibility study, we used cross-sectional data to create a clinical dashboard to calculate and display the relation between BMI and EOSS and the prevalence of related comorbidities. We obtained data from the Northern Alberta Primary Care Research Network and the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). We included patients at least 18 years of age with BMI between 30 and 60 who visited a network clinic between July 2016 and July 2019. We calculated descriptive statistics and used stepwise ordinary least squares regression to assess the contributions of age, sex and BMI to EOSS variation. RESULTS: We created a clinical dashboard using the CPCSSN data presentation tool. Of the total 31 496 patients included in the study, 23 460 had a BMI of at least 30; BMI was unavailable for 8036 patients. Within each EOSS disease severity stage, there were similar proportions of patients from each BMI class (e.g., patients with EOSS stage 2 included 51.8% of those with BMI class I, 55.3% of those with BMI class II and 58.8% of those with BMI class III). INTERPRETATION: Using data from primary care electronic medical records, it was feasible to create a clinical dashboard for obesity that highlighted the severity and stage of obesity. Making this information easily accessible for individual clinical care and practice-level quality improvement may advance obesity care.

Malformation risk of new anti-epileptic drugs in women with epilepsy; observational data from the Kerala registry of epilepsy and pregnancy (KREP).

OBJECTIVES: We aim to report the major congenital malformation (MCM) rates for new and old anti-epileptic drugs (AED) exposures during the first trimester of pregnancy in women with epilepsy (WWE). METHODS: We extracted relevant data on drug exposure and malformation rate from the records of a prospective observational registry (Kerala Registry of Epilepsy and Pregnancy) for all completed pregnancies between 1998 and 2019. A comprehensive and uniform criterion with detailed guideline was used for assessment of malformations. We employed generalised linear model to generate adjusted incidence rate ratios (aIRR) of MCM in AED exposed group as compared to AED unexposed group, after adjustment for age and educational status of mothers' and epilepsy classification. RESULTS: The unadjusted MCM rate was 6.2% for all the infants included in the study (148/2328); 4.7% for the unexposed group (16/340), and 6.6% for the exposed group (132/1988). The aIRR of MCM as compared to unexposed group was similar for all monotherapies; lamotrigine (0.50; 95% CI 0.07-3.68), levetiracetam (1.16; 0.43-3.11), oxcarbazepine (1.61; 0.62-4.21) valproate (1.71, 0.93-3.19), phenytoin (1.21, 0.51-2.90), carbamazepine (0.99, 0.54-1.82), and phenobarbitone (1.20, 0.52-2.74). However, the point estimates suggest least risk with lamotrigine and highest risk with valproate. Polytherapy with high-dose valproate carried significantly higher risk of MCM as compared to the unexposed group (aIRR=4.12; 2.18-7.79, p<0.001). The aIRR of GTCS during pregnancy was 1.63 (95% CI 1.12-2.37, p = 0.011) for monotherapy with new AEDs (lamotrigine, levetiracetam or oxcarbazepine) as compared to old AEDs (phenobarbitone, phenytoin, carbamazepine, or valproate). CONCLUSION: The MCM risk was significantly higher for polytherapy with high dose valproate. It did not differ substantially between different AED monotherapies although point estimate was lowest with lamotrigine. Pregnant women on new AEDs report higher likelihood of GTCS than women on old AEDs during pregnancy.

Complications of Lung Transplantation: Update on Imaging Manifestations and Management.

As lung transplantation has become the most effective definitive treatment option for end-stage chronic respiratory diseases, yearly rates of this surgery have been steadily increasing. Despite improvement in surgical techniques and medical management of transplant recipients, complications from lung transplantation are a major cause of morbidity and mortality. Some of these complications can be classified on the basis of the time they typically occur after lung transplantation, while others may occur at any time. Imaging studies, in conjunction with clinical and laboratory evaluation, are key components in diagnosing and monitoring these conditions. Therefore, radiologists play a critical role in recognizing and communicating findings suggestive of lung transplantation complications. A description of imaging features of the most common lung transplantation complications, including surgical, medical, immunologic, and infectious complications, as well as an update on their management, will be reviewed here. Keywords: Pulmonary, Thorax, Surgery, Transplantation Supplemental material is available for this article. © RSNA, 2021.

Visual detection thresholds in the Asian honeybee, Apis cerana.

To understand how insect pollinators find flowers against complex backgrounds in diverse natural habitats, it is required to accurately estimate the thresholds for target detection. Detection thresholds for single targets vary between bee species and have been estimated in the Western honeybee, a species of bumblebee and in a stingless bee species. We estimated the angular range of detection for coloured targets in the Asian honeybee Apis cerana. Using a Y-maze experimental set up, we show that targets that provided both chromatic and green receptor contrast were detected at a minimum visual angle of 7.7°, while targets with only chromatic contrast were detected at a minimum angle of 13.2°. Our results thus provide a robust foundation for future studies on the visual ecology of bees in a comparative interspecific framework.