Practical Synthesis of Terminal Vinyl Fluorides.

The synthesis of di- and trisubstituted vinyl fluorides with high isomeric purity remains a challenge for organic synthesis. While many methods exist to access these compounds, the separation of the desired isomer from the minor isomer and/or starting materials often is difficult. Herein, we report a practical method to access di- and trisubstituted vinyl fluorides via a selective Horner-Wadsworth-Emmons olefination/hydrolysis, which provides crystalline 2-fluoroacrylic acids in high (>98%) E-isomeric purity. A subsequent silver-catalyzed stereoretentive decarboxylation provides the title substances with high isomeric purity and without the need for tedious chromatography to remove the minor isomer. The process was amenable to a variety of aldehydes and ketones and provided a diverse array of di- and trisubstituted vinyl fluorides. The sequence was applied to the synthesis of antibacterial and anti-inflammatory compounds.

Caregiving Across International Borders: a Systematic Review of Literature on Transnational Carer-Employees.

In diaspora and transnational studies little is known about the experiences of transnational carer-employees (TCEs). TCEs provide unpaid/informal care across international borders to an adult family member, friend, or relative with disability and/or age-related needs, while also working in paid employment in the country of resettlement. The primary focus of this systematic review was to examine how cultural and historical elements of transnational caregiving influence the economic, social, and health/well-being of TCEs. This systematic review draws on quantitative and qualitative peer-reviewed literature on TCEs' experiences from Canada, the USA, or Australia between 1997 and 2017. In all, 16 articles that fulfilled the search inclusion criteria were selected. The articles were analyzed using content and thematic analysis. The review highlighted that transnational caregiving is a multi-dimensional phenomenon. There is a reciprocal relationship between adult children providing care to their parents and parents helping their children resettle in their new home. The findings suggest that TCEs provide practical, financial, and emotional care to their families abroad. To the best of our knowledge, this is the first comprehensive systematic review of the experiences of TCEs. Increasingly complex immigration experiences of transnational families require innovative policy responses from a transnational and intersectionality lens. Immigrants need support to maintain solid transnational networks and simultaneously adapt to the country of resettlement. Employers can use the findings to support TCEs in balancing unpaid care across vast geographical distances while sustaining their economic and social well-being.

Insights into patient characteristics and documentation of the use of sedative-hypnotic/anxiolytics in primary care: a retrospective chart review study.

BACKGROUND: Despite the known safety risks of long-term use of sedative-hypnotic/anxiolytic medications, there has been limited guidance for the safe and effective use of their chronic use in a primary care clinic setting. Understanding the characteristics of patients who receive sedative-hypnotic/anxiolytic medication and the clinical documentation process in primary care is the first step towards understanding the nature of the problem and will help inform future strategies for clinical research and practice. OBJECTIVES: Characterize patients who received a sedative-hypnotic/anxiolytic prescription in primary care, and (2) gain an understanding of the clinical documentation of sedative-hypnotic/anxiolytic indication and monitoring in electronic medical records (EMR). METHODS: A random selection of patients who received a prescription for a benzodiazepine or Z-drug hypnotic between January 2014 and August 2016 from four primary care clinics in Winnipeg were included. Data was collected retrospectively using the EMR (Accuro®). Patient variables recorded included sex, age, comorbidities, medications, smoking status, and alcohol status. Treatment variables included drug type, indication, pattern of use, dose, adverse events, psychosocial intervention, tapering attempts, social support, life stressor, and monitoring parameters for sedative-hypnotic use. Demographic and clinical characteristics were described using descriptive statistics. RESULTS: Records from a sample of 200 primary care patients prescribed sedative-hypnotic/anxiolytics were analyzed (mean age 55.8 years old, 61.5% ≥ 65 years old, 61.0% female). Long-term chronic use (≥ 1 year) of a sedative-hypnotic/anxiolytic agent was observed in 29.5% of the sample. Zopiclone (30.7%) and lorazepam (28.7%) were the most common agents prescribed. Only 9.5% of patients had documentation of a past tapering attempt of their sedative-hypnotic/anxiolytic. The most common indications for sedative-hypnotic/anxiolytic use recorded were anxiety (33.0%) and sleep (18.0%), but indication was undetermined for 57.0% of patients. Depression (33.5%) and falls (18.5%) were reported by patients after the initiation of these agents. CONCLUSIONS: A higher proportion of females and users 65 years and older received a prescription for a sedative-hypnotic/anxiolytic, consistent with previous studies on sedative-hypnotic use. We found inconsistencies in the documentation surrounding sedative-hypnotic/anxiolytic use. The indication for their use was unclear in a large number of patients. These findings will help us understand the state of the problem in primary care and inform future strategies for clinical research.

Outcomes of assistance dog placement in the home for individuals with autism spectrum disorder and their families: A pilot study.

INTRODUCTION: Evidence indicates that assistance dogs placed in the home are effective in supporting individuals with Autism Spectrum Disorder (ASD) by increasing social and community participation and promoting quality of life. This study aimed to examine the outcomes of assistance dog placement on quality of life, independence, and participation of families including individuals with ASD placed with an assistance dog compared to families on the waiting list for an autism assistance dog and to evaluate the feasibility of the design for future studies. METHODS: A cross-sectional comparative study was conducted. The Adaptive Behaviour Analysis System, Social Responsiveness Scale, Autism Treatment Evaluation Checklist, Canadian Occupational Performance Measure, and Autism Family Experience Questionnaire were used to evaluate adaptive skills, behaviour, social difficulties, daily functioning, and family quality of life. RESULTS: Six families who had an autism assistance dog placed with them, and 12 families who were on the waiting list were recruited using purposeful sampling. The pilot data found no significant differences between the two groups. However, trends were observed which suggested that assistance dogs can increase desired social behaviours, decrease ASD severity, and improve family wellbeing. For families with an assistance dog, more positive outcomes were observed for families who were partnered with an assistance dog for longer. Parents (and sometimes individuals with ASD) were able to complete and return the outcome measures via mail to collect the outcome data for the study. CONCLUSION: These study findings add to the developing evidence about the use of assistance dogs with this population. A larger sample size may have allowed for significant associations to be detected. The methods used were feasible to be applied in a larger study. These results may assist health professionals advocate for funding for assistance dog placement to individuals with ASD and their families.

The effect of synthetic female sex pheromone on the transmission of the fungus Metarhizium brunneum by male Agriotes obscurus click beetles.

Autodissemination techniques can potentially be used to distribute insecticides, including microbial insecticides, to cryptic pests. This approach is reliant on the target insect either passing the pathogen passively to other insects or the pathogen cycling within the population after the initial host dies. Here we examine, in small scale experiments, whether male Agriotes obscurus click beetles passively transmit the spores of the fungus Metarhizium brunneum directly, or indirectly via the environment, and whether this is influenced by exposure to synthetic female pheromone. We found that the beetles did not avoid M. brunneum spores and that this behaviour was not affected by pheromone. Exposure to pheromone increased beetle movement and uptake of spores, but this did not result in an increase in infected beetles under our conditions. Beetles were able to transfer spores at high levels via environmental contamination. However, contamination of the environment declined rapidly after exposure to the spores. The results are discussed in the context of developing an autodissemination strategy for click beetles.

Effect of Collection Month, Visible Light, and Air Movement on the Attraction of Male Agriotes obscurus L. (Coleoptera: Elateridae) Click Beetles to Female Sex Pheromone.

Elaterid female sex pheromone, while currently used for monitoring the adult life stage (click beetle), has only recently been explored as a potential management tool. Consequently, there is little understanding of how abiotic and biotic conditions influence the response of click beetles to the pheromone. We examined whether the response of male Agriotes obscurus L. (Coleoptera: Elateridae) beetles to a cellulose-based formulation of female sex pheromone ('pheromone granules') is influenced by air movement, presence of visible light, and month of beetle collection. In addition, we investigated the distance from which beetles were attracted to the pheromone granules. Click beetle response was determined by measuring movement parameters in free-walking arena experiments. The response to pheromone was not affected by the presence or absence of visible light. We found that beetles collected earlier in the season had increased activity and interaction with pheromone under moving air conditions, compared to beetles collected later. When controlling for storage time, we confirmed that individuals collected in May were less active than beetles collected in March and April. In the field, beetles were recaptured from up to 14 m away from a pheromone granule source, with over 50% being recovered within 4.4 h from a distance of 7 m or less. Understanding how abiotic and biotic factors affect pest response to pheromone can lead to more effective and novel uses of pheromone-based management strategies.

Effects of Ving Tsun sticking-hand training on upper-limb sensorimotor performance in community-dwelling middle-aged and older adults: A randomized controlled trial.

OBJECTIVE: To evaluate the effects of Ving Tsun (VT) sticking-hand training on upper-limb joint position sense and muscular performance in community-dwelling middle-aged and older adults. METHODS: Thirty-three adults were randomly allocated to either a VT group or a control group. The VT group received VT sticking-hand training twice per week for 3 months. Measurements were taken before and after the intervention period. The primary outcome was elbow-joint repositioning error, which was measured by an elbow-joint passive positioning and active repositioning test using a universal goniometer. Secondary outcomes were upper-limb muscles' peak force and time taken to reach peak force as measured by a hand-held dynamometer. RESULTS: No significant time, group or time-by-group interaction effects were found for elbow-joint repositioning error or upper-limb muscle peak force outcomes. Shoulder flexor time to peak force decreased by 33.8% from pre-test to post-test in the VT group (P = 0.007). Shoulder abductor, internal and external rotator, and elbow extensor times to peak force decreased by 30.0%-35.9% in the VT group (P < 0.05) and by 30.4%-37.1% in the control group (P < 0.05). CONCLUSIONS: VT sticking-hand training does not improve elbow-joint position sense or the maximum strength of upper-limb muscles in middle-aged and older adults. However, VT can improve shoulder flexor muscles' time to reach peak force in these populations. VT had no obvious effect on the time required to reach peak force in other shoulder muscles and elbow extensors.

Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors.

The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macrocyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.

A versatile catalyst system for enantioselective synthesis of 2-substituted 1,4-benzodioxanes.

We report the synthesis of enantiomerically enriched 1,4-benzodioxanes containing alkyl, aryl, heteroaryl, and/or carbonyl substituents at the 2-position. The starting 1,4-benzodioxines were readily synthesized via ring closing metathesis using an efficient nitro-Grela catalyst at ppm levels. Excellent enantioselectivities of up to 99:1 er were obtained by using the versatile catalyst system [Ir(cod)Cl]2/BIDIME-dimer in the asymmetric hydrogenation of 2-substituted 1,4-benzodioxines. Furthermore, DFT calculations reveal that the selectivity of the process is controlled by the protonation step; and coordinating groups on the substrate may alter the interaction with the catalyst, resulting in a change in the facial selectivity.

Copper-catalyzed asymmetric hydrogenation of 2-substituted ketones via dynamic kinetic resolution.

A new class of tunable heterophosphole dimeric ligands have been designed and synthesized. These ligands have enabled the first examples of Cu-catalyzed hydrogenation of 2-substituted-1-tetralones and related heteroaryl ketones via dynamic kinetic resolution, simultaneously creating two contiguous stereogenic centers with up to >99 : 1 dr and 98 : 2 er. The ligand-Cu complexes were isolated and characterized by single crystal X-ray, and DFT calculations revealed a novel heteroligated dimeric copper hydride transition state.

An evaluation of the objective quality and perceived usefulness of maternity clinical practice guidelines at a tertiary maternity unit.

BACKGROUND: Compliance with maternity clinical practice guidelines developed by National Women's Health has been found to be low at audit. OBJECTIVE: To explore the reasons for poor compliance with maternity guidelines by evaluating the quality of a sample of National Women's Health guidelines using a validated instrument and assessing local guideline users' perceptions of and attitudes toward guidelines. DESIGN: Five independent reviewers evaluated the quality of 10 purposively selected guidelines for adherence to the Appraisal of Guidelines Research & Evaluation (AGREE) II instrument standards. A self-administered questionnaire for staff was undertaken regarding views of and barriers to guideline use. RESULTS: None of the guidelines attained a score over 50% for the following domains: stakeholder involvement, rigour of development, applicability, editorial independence. The highest scoring domain was clarity of presentation (mean 69%). All guidelines scored the minimum possible for editorial independence. Survey respondents had positive attitudes toward guidelines, believed that their use could improve quality of care within the service, and felt that encouragement from senior staff members and peers would encourage their use. Accessibility was the most commonly cited of many barriers identified. CONCLUSION: The National Women's Health guidelines evaluated in this study cannot be considered to be high quality, and could be improved by reporting on methodology of the development process. Although poor guideline development may contribute to failure of the local maternity guidelines, it appears that accessibility is a major barrier to their use and implementation.

Association of long-term glycaemic control on tear break-up times and dry eye symptoms in Chinese patients with type 2 diabetes.

IMPORTANCE: Diabetes mellitus is known to be associated with dry eye syndrome (DES), but the effects of long-term glycaemic control on tear film metrics and dry eye symptoms are not known in the Chinese population. BACKGROUND: To evaluate tear film stability and dry eye symptoms and their associations with systemic risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital), Hong Kong. PARTICIPANTS: A total of 80 Chinese participants, aged 18 or above, with T2DM recruited from the specialist outpatient setting were included. METHODS: The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI). The association between OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using multiple linear regression. MAIN OUTCOME MEASURES: The associations between long-term glycaemic control and NITBUT and OSDI scores. RESULTS: Stepwise multiple linear regression analysis revealed glycated haemoglobin to be the only significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2 = 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM population. The odds of DES for increasing percentage of glycated haemoglobin was 1.49 (95% confidence interval: 1.03-2.17, P = 0.04). CONCLUSIONS AND RELEVANCE: Our findings highlight the importance of good glycaemic control as a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM.

Bone Mineral Density, Balance Performance, Balance Self-Efficacy, and Falls in Breast Cancer Survivors With and Without Qigong Training: An Observational Study.

PURPOSE: A deterioration in bone strength and balance performance after breast cancer treatment can result in injurious falls. Therefore, interventions need to be developed to improve the bone strength and balance ability of breast cancer survivors. This cross-sectional exploratory study aimed to compare the bone mineral density (BMD), balance performance, balance self-efficacy, and number of falls between breast cancer survivors who practiced qigong, breast cancer survivors who did not practice qigong, and healthy individuals. METHODS: The study included 40 breast cancer survivors with more than 3 months of qigong experience, 17 breast cancer survivors with no qigong experience, and 36 healthy controls. All the participants underwent dual-energy X-ray absorptiometry scans to measure their lumbar spine, total hip, femoral neck, and total radius BMDs. The participants also underwent a timed one-leg stand test to measure their single-leg standing balance. The participants' balance self-efficacy was assessed using the activities-specific balance confidence scale, and the number of falls experienced by each participant was assessed in a face-to-face interview. RESULTS: The lumbar spine, total hip, femoral neck, and total radius BMDs were similar between the 3 groups ( P > .05). The breast cancer-qigong group outperformed the breast cancer-control group by 27.3% when they performed the one-leg stand test on a foam surface ( P = .025), and they also had a higher balance self-efficacy score ( P = .006). Nevertheless, the numbers of falls were comparable between the 3 groups ( P > .05). CONCLUSION: Qigong may be a suitable exercise for improving the balance performance and balance self-efficacy of breast cancer survivors.

Total Synthesis of (±)-Phomoidride†D.

Described herein is a synthetic strategy for the total synthesis of (±)-phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels-Alder cycloaddition. A subsequent SmI2 -mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.

Early Cerebral Infarction after Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a serious disease with high case fatality and morbidity. Early cerebral infarction has been suggested as a risk factor for poor outcome. We aimed to assess the pattern of early and delayed cerebral infarction after aneurysmal subarachnoid hemorrhage. We prospectively enrolled consecutive aneurysmal subarachnoid hemorrhage (SAH) patients presenting to an academic neurosurgical referral center (Prince of Wales Hospital, the Chinese University of Hong Kong) in Hong Kong. Cerebral infarction occurred in 24 (48 %) patients, in which 14 (28 %) had early cerebral infarction and 14 (28 %) had delayed cerebral infarction. Early anterior cerebral infarction occurred in a similar proportion of anterior and posterior circulation aneurysms (24 % vs. 21 %), whereas posterior circulation aneurysm patients had a higher proportion of early posterior cerebral infarction compared with anterior circulation aneurysm patients (18 % vs. 2 %). In conclusion, early cerebral infarction was common and different from delayed cerebral infarction.

Effect of upright position on tonsillar level in adolescent idiopathic scoliosis.

PURPOSE: The aim of this study was to investigate the effect of an upright position on cerebellar tonsillar level in patients with adolescent idiopathic scoliosis (AIS). METHODS: Twenty-five patients with clinically diagnosed AIS and 18 normal controls were examined in both supine and upright positions using 0.25T MRI. The position of the inferior cerebellar tonsil tip relative to a reference line connecting the basion to the opisthion (BO line) was measured in millimetres. RESULTS: None of the 18 normal control subjects had cerebellar tonsillar descent below the BO line in either supine or the upright position. Forty-eight percent of AIS patients had tonsillar descent in the upright position, compared to 28 % in the supine position. In the upright position, cerebellar tonsillar position was lower in AIS patients than in normal subjects (mean -0.7 ± 1.5 vs. +2.1 ± 1.7, p < 0.00001). AIS patients also had a large degree of tonsillar excursion between upright and supine positions compared to normal subjects (mean -1.9 ± 2.3 vs. -0.1 ± 0.2, p < 0.00001). CONCLUSIONS: When considering the theoretical likelihood that a low tonsillar position may affect spinal cord function, one should bear in mind that tonsillar descent in AIS is significantly greater in the upright position. KEY POINTS: • AIS patients exhibited greater cerebellar tonsillar descent in upright than supine position. • Cerebellar tonsillar position was lower in AIS patients than normal subjects. • AIS patients exhibited greater tonsillar excursion between supine and upright positions.

Diagnostic capability of low- versus high-field magnetic resonance imaging for lumbar degenerative disease.

STUDY DESIGN: Cohort study. OBJECTIVE: To investigate the diagnostic capability of low-field magnetic resonance imaging (MRI) compared with high-field MRI for degenerative disease of the lumbar spine. SUMMARY OF BACKGROUND DATA: Low-field MRI has several advantages over high-field magnetic resonance systems (easier installation, lower purchase, and maintenance cost). The diagnostic capability of low-field MRI for degenerative disease of the lumbar spine has not been compared with that of high-field MRI. METHODS: Hundred patients (mean age: 56.3 yr, range: 32-80; F:M = 59:41) with neurogenic claudication or sciatica were studied. All patients underwent MRI of the lumbar spine on both low-field (0.25T) and high-field (1.5T or 3.0T) magnetic resonance systems. Intervertebral disc herniation, central canal, lateral recess, and exit foraminal stenosis as well as nerve root compression at L3-L4, L4-L5, and L5-S1 were evaluated by 2 radiologists for both low- and high-field systems using established reliable grading systems. RESULTS: There was excellent agreement between low- and high- field MRI with regard to grading the presence and severity of disc herniation (r = 0.92-0.94; P < 0.05), central canal stenosis (r = 0.89-0.91; P < 0.05), lateral recess stenosis (r = 0.81-0.87; P < 0.05), and exit foramen stenosis (r = 0.81-0.89; P < 0.05). Descending or exiting nerve root compression occurred in 52% of patients at L3-L4, L4-L5, or L5-S1 levels, with good agreement between low-field and high-field MRI (r = 0.71-0.76; P < 0.05) for nerve root compression. CONCLUSION: Excellent reliability between low- and high- field MRI was found for most features of lumbar disc degeneration, with good agreement for nerve root compression. 0.25T MRI was more susceptible to motion artifact, probably due to longer scanning time. LEVEL OF EVIDENCE: 3.

Preliminary investigation on prevalence of osteoporosis and osteopenia: Should we tune our focus on healthy adults?

AIM: Osteoporosis and osteopenia are global health problems with increasing trend, particularly in developed regions. Apart from traditional well-recognized high-risk groups (i.e. postmenopausal women and elders), prevalence of such problems among adults should not be ignored because of the advantages of early detection and health promotion. Therefore, this preliminary study aims to investigate the prevalence of osteoporosis and osteopenia among adult office workers, which represented a relatively large proportion of the population in urbanized cities. METHODS: An GE-Lunar Achilles ultrasonometer was used to screen the bone mineral density (BMD) of 80 participants. RESULTS: The BMD T-score ranged from -3 to 3.5. The majority of the participants had normal BMD result (T-score, ≥ -1), whereas 35% was classified as abnormal (T-score, < -1) including 31.3% osteopenia and 3.8% osteoporosis. CONCLUSION: High prevalence rate of abnormal BMD among healthy adults should be further studied in this population. The findings also suggest that the current ignorance in adulthood may increase the prevalence of osteoporotic fractures in the future.

Balance Performance in Irradiated Survivors of Nasopharyngeal Cancer with and without Tai Chi Qigong Training.

This cross-sectional exploratory study aimed to compare the one-leg-stance time and the six-minute walk distance among TC Qigong-trained NPC survivors, untrained NPC survivors, and healthy individuals. Twenty-five survivors of NPC with TC Qigong experience, 27 survivors of NPC without TC Qigong experience, and 68 healthy individuals formed the NPC-TC Qigong group, NPC-control group, and healthy-control group, respectively. The one-leg-stance (OLS) timed test was conducted to assess the single-leg standing balance performance of the participants in four conditions: (1) standing on a stable surface with eyes open, (2) standing on a compliant surface with eyes open, (3) standing on a stable surface with eyes closed, and (4) standing on a compliant surface with eyes closed. The six-minute walk test (6MWT) was used to determine the functional balance performance of the participants. Results showed that the NPC-control group had a shorter OLS time in all of the visual and supporting surface conditions than the healthy control group (P < 0.05). The OLS time of the TC Qigong-NPC group was comparable to that of the healthy control group in the somatosensory-challenging condition (condition 3) (P = 0.168) only. Additionally, there was no significant difference in the 6MWT distance among the three groups (P > 0.05). TC Qigong may be a rehabilitation exercise that improves somatosensory function and OLS balance performance among survivors of NPC.