Installing the "magic methyl" - C-H methylation in synthesis

The selective and efficient C-H methylation of sp2 and sp3 carbon centres has become a powerful transformation in the synthetic toolbox. Due to the potential for profound changes to physicochemical properties attributed to the installation of a "Magic Methyl" group at a strategic site in a lead compound, such techniques have become highly desirable in modern drug discovery and synthesis programmes. This review will cover the diverse techniques that have been employed to enable the selective installation of the C-Me bond in a wide range of chemical structures, from simple building blocks to complex drug-like architectures

Field Theory for a Deuteron Quantum Liquid

Based on general symmetry principles we study an effective Lagrangian for a neutral system of condensed spin-1 deuteron nuclei and electrons, at greater-than-atomic but less-than-nuclear densities. We expect such matter to be present in thin layers within certain low-mass brown dwarfs. It may also be produced in future shock-wave-compression experiments as an effective fuel for laser induced nuclear fusion. We find a background solution of the effective theory describing a net spin zero condensate of deuterons with their spins aligned and anti-aligned in a certain spontaneously emerged preferred direction. The spectrum of low energy collective excitations contains two spin waves with linear dispersions -- like in antiferromagnets -- as well as gapped longitudinal and transverse modes related to the Meissner effect -- like in superconductors. We show that counting of the Nambu-Goldstone modes of spontaneously broken internal and space-time symmetries obeys, in a nontrivial way, the rules of the Goldstone theorem for Lorentz non-invariant systems. We discuss thermodynamic properties of the condensate, and its potential manifestation in the low-mass brown dwarfs.Comment: 19 LaTeX pages; v2: 2 refs added, JHEP versio

The role of tibialis posterior fatigue on foot kinematics during walking

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate the effect of localised tibialis posterior muscle fatigue on foot kinematics during walking. It was hypothesised that following fatigue, subjects would demonstrate greater forefoot and rearfoot motion during walking. It was also postulated that the magnitude of the change in rearfoot motion would be associated with standing anatomical rearfoot posture.</p> <p>Methods</p> <p>Twenty-nine subjects underwent an exercise fatigue protocol aimed at reducing the force output of tibialis posterior. An eight camera motion analysis system was used to evaluate 3D foot kinematics during treadmill walking both pre- and post-fatigue. The anatomical rearfoot angle was measured during standing prior to the fatigue protocol using a goniometer.</p> <p>Results</p> <p>Peak rearfoot eversion remained unchanged following the fatigue protocol. Although increases in rearfoot eversion excursion were observed following fatigue, these changes were of a magnitude of questionable clinical significance (<1.0°). The magnitude of the change in rearfoot eversion due to fatigue was not associated with the anatomical measurement of standing rearfoot angle. No substantial changes in forefoot kinematics were observed following the fatigue protocol.</p> <p>Conclusions</p> <p>These data indicate that reduced force output of the tibialis posterior muscle did not alter rearfoot and forefoot motion during gait. The anatomical structure of the rearfoot was not associated with the dependence of muscular activity that an individual requires to maintain normal rearfoot kinematics during gait.</p

The counseling african americans to control hypertension (caatch) trial: baseline demographic, clinical, psychosocial, and behavioral characteristics

<p>Abstract</p> <p>Background</p> <p>Effectiveness of combined physician and patient-level interventions for blood pressure (BP) control in low-income, hypertensive African Americans with multiple co-morbid conditions remains largely untested in community-based primary care practices. Demographic, clinical, psychosocial, and behavioral characteristics of participants in the Counseling African American to Control Hypertension (CAATCH) Trial are described. CAATCH evaluates the effectiveness of a multi-level, multi-component, evidence-based intervention compared with usual care (UC) in improving BP control among poorly controlled hypertensive African Americans who receive primary care in Community Health Centers (CHCs).</p> <p>Methods</p> <p>Participants included 1,039 hypertensive African Americans receiving care in 30 CHCs in the New York Metropolitan area. Baseline data on participant demographic, clinical (<it>e.g</it>., BP, anti-hypertensive medications), psychosocial (<it>e.g</it>., depression, medication adherence, self-efficacy), and behavioral (<it>e.g</it>., exercise, diet) characteristics were gathered through direct observation, chart review, and interview.</p> <p>Results</p> <p>The sample was primarily female (71.6%), middle-aged (mean age = 56.9 ± 12.1 years), high school educated (62.4%), low-income (72.4% reporting less than $20,000/year income), and received Medicaid (35.9%) or Medicare (12.6%). Mean systolic and diastolic BP were 150.7 ± 16.7 mm Hg and 91.0 ± 10.6 mm Hg, respectively. Participants were prescribed an average of 2.5 ± 1.9 antihypertensive medications; 54.8% were on a diuretic; 33.8% were on a beta blocker; 41.9% were on calcium channel blockers; 64.8% were on angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs). One-quarter (25.6%) of the sample had resistant hypertension; one-half (55.7%) reported medication non-adherence. Most (79.7%) reported one or more co-morbid medical conditions. The majority of the patients had a Charlson Co-morbidity score ≥ 2. Diabetes mellitus was common (35.8%), and moderate/severe depression was present in 16% of participants. Participants were sedentary (835.3 ± 1,644.2 Kcal burned per week), obese (59.7%), and had poor global physical health, poor eating habits, high health literacy, and good overall mental health.</p> <p>Conclusions</p> <p>A majority of patients in the CAATCH trial exhibited adverse lifestyle behaviors, and had significant medical and psychosocial barriers to adequate BP control. Trial outcomes will shed light on the effectiveness of evidence-based interventions for BP control when implemented in real-world medical settings that serve high numbers of low-income hypertensive African-Americans with multiple co-morbidity and significant barriers to behavior change.</p

Cohort Randomised Controlled Trial of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People (The REFORM Trial)

BACKGROUND: Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. DESIGN: Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. RESULTS: In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of £30,000 per QALY gained. CONCLUSION: There was a small reduction in falls. The intervention may be cost-effective. TRIAL REGISTRATION: ISRCTN ISRCTN68240461

The REFORM study protocol: a cohort randomised controlled trial of a multifaceted podiatry intervention for the prevention of falls in older people

Introduction: Falls and fall-related injuries are a serious cause of morbidity and cost to society. Foot problems and inappropriate footwear may increase the risk of falls; therefore podiatric interventions may play a role in reducing falls. Two Cochrane systematic reviews identified only one study of a podiatry intervention aimed to reduce falls, which was undertaken in Australia. The REFORM trial aims to evaluate the clinical and cost-effectiveness of a multifaceted podiatry intervention in reducing falls in people aged 65 years and over in a UK and Irish setting. Methods and analysis: This multicentre, cohort randomised controlled trial will recruit 2600 participants from routine podiatry clinics in the UK and Ireland to the REFORM cohort. In order to detect a 10% point reduction in falls from 50% to 40%, with 80% power 890 participants will be randomised to receive routine podiatry care and a falls prevention leaflet or routine podiatry care, a falls prevention leaflet and a multifaceted podiatry intervention. The primary outcome is rate of falls (falls/person/time) over 12 months assessed by patient self-report falls diary. Secondary self-report outcome measures include: the proportion of single and multiple fallers and time to first fall over a 12-month period; Short Falls Efficacy Scale—International; fear of falling in the past 4 weeks; Frenchay Activities Index; fracture rate; Geriatric Depression Scale; EuroQoL-five dimensional scale 3-L; health service utilisation at 6 and 12 months. A qualitative study will examine the acceptability of the package of care to participants and podiatrists. Ethics and dissemination: The trial has received a favourable opinion from the East of England—Cambridge East Research Ethics Committee and Galway Research Ethics Committee. The trial results will be published in peer-reviewed journals and at conference presentations. Trial registration number: Current Controlled Trials ISRCTN68240461assigned 01/07/2011

Hypertension and type 2 diabetes: What family physicians can do to improve control of blood pressure - an observational study

Background: The prevalence of type 2 diabetes is rising, and most of these patients also have hypertension, substantially increasing the risk of cardiovascular morbidity and mortality. The majority of these patients do not reach target blood pressure levels for a wide variety of reasons. When a literature review provided no clear focus for action when patients are not at target, we initiated a study to identify characteristics of patients and providers associated with achieving target BP levels in community-based practice. Methods: We conducted a practice- based, cross-sectional observational and mailed survey study. The setting was the practices of 27 family physicians and nurse practitioners in 3 eastern provinces in Canada. The participants were all patients with type 2 diabetes who could understand English, were able to give consent, and would be available for follow-up for more than one year. Data were collected from each patient’s medical record and from each patient and physician/nurse practitioner by mailed survey. Our main outcome measures were overall blood pressure at target (< 130/80), systolic blood pressure at target, and diastolic blood pressure at target. Analysis included initial descriptive statistics, logistic regression models, and multivariate regression using hierarchical nonlinear modeling (HNLM). Results: Fifty-four percent were at target for both systolic and diastolic pressures. Sixty-two percent were at systolic target, and 79% were at diastolic target. Patients who reported eating food low in salt had higher odds of reaching target blood pressure. Similarly, patients reporting low adherence to their medication regimen had lower odds of reaching target blood pressure. Conclusions: When primary care health professionals are dealing with blood pressures above target in a patient with type 2 diabetes, they should pay particular attention to two factors. They should inquire about dietary salt intake, strongly emphasize the importance of reduction, and refer for detailed counseling if necessary. Similarly, they should inquire about adherence to the medication regimen, and employ a variety of patient-oriented strategies to improve adherence

Older People, Sense of Coherence and Community

Population ageing is a global trend and even though years added to life often are lived in good health; it will have an impact on healthcare, housing and facilities, and social security costs. Healthy ageing in place, especially in one’s own home and community, increasingly receives attention from health professionals, researchers, and policymakers. In this chapter, we first discuss the meaning of the concept of healthy ageing, and how Sense of Coherence contributes to this process. Next, we discuss the characteristics of the community in which older people live their lives and how the community can provide resources (GRR and SRR) to strengthen Sense of Coherence and hence perceived well-being and quality of life

Carbocyanine Dye Usage in Demarcating Boundaries of the Aged Human Red Nucleus

Background: Though the adult human magnocellular Red nucleus (mNr) is essentially vestigial and its boundaries with neighbouring structures have never been well demarcated, human studies in utero have shown a well developed semilunar mNr wrapping around the caudal parvicellular Red nucleus (pNr), similar to what is seen in quadrupeds. In the present study, we have sought to better delineate the morphological determinants of the adult human Red nucleus (ahRn). Methods and Findings: Serial sections of ahRn show fine myelinated fibers arising from pNr and turning toward the central tegmental tract. DiI was deposited within a well restricted region of ahRn at the fasciculus retroflexus level and the extent of label determined. Nissl-stained serial sections allowed production of a 3-D mNr model, showing rudimentary, vestigial morphology compared with its well developed infant homologue. DiI within this vestigial mNr region at the level of the oculomotor nerve showed labeled giant/large mNr neurons, coarse fiber bundles at the ventral tegmental decussation and lateral lemniscal label. Conclusions: Large amounts of DiI and a long incubation time have proven useful in aged human brain as a marker of long axons and large cell bodies of projecting neurons such as the rubrospinal projection and for clarifying nuclear boundaries of closed nuclei (e.g., the large human pNr). Our 3D model of adult human mNr appeared shrunken in shape and axiall