Effects of donation frequency on U.S. source plasma donor health.

Background: Plasma-derived medicinal products (PDMPs) are essential, life-saving medicines manufactured from plasma donated by healthy human volunteers. PDMPs are used to treat a range of rare, serious, and chronic conditions, often genetic in origin. Approximately 70% of the Source Plasma (SP) used for PDMP manufacturing comes from United States (US).

Guiding principles for rewilding.

There has been much recent interest in the concept of rewilding as a tool for nature conservation, but also confusion over the idea, which has limited its utility. We developed a unifying definition and 10 guiding principles for rewilding through a survey of 59 rewilding experts, a summary of key organizations' rewilding visions, and workshops involving over 100 participants from around the world. The guiding principles convey that rewilding exits on a continuum of scale, connectivity, and level of human influence and aims to restore ecosystem structure and functions to achieve a self-sustaining autonomous nature.

Patient-reported reasons for delay in diagnosis of age-related macular degeneration: a national survey.

Objectives: To investigate whether people with age-related macular degeneration (AMD) are able to self-detect symptoms and, if so, what symptoms they experience, from whom they first seek help, whether help is sought within the 1 week recommended by the Royal College of Ophthalmologists' guidelines and reasons for any delay.

Methods And Analysis: A retrospective, cross-sectional survey design. Postal surveys were sent to 4000 members of the UK Macular Society.

A new approach to iliac bone histomorphometry: implications for biomechanics and cell biology.

I devised a method for obtaining information on cancellous bone structure from iliac bone histomorphometry that led to the demonstration that architecture is an important component of bone strength and bone fragility. Furthermore, this method contributed to the recognition of the importance of changes in osteoclast and osteocyte apoptosis in response to estrogen deficiency and replacement.

For whom the bell tolls: distress signals from long-lived osteocytes and the pathogenesis of metabolic bone diseases.

Osteocytes are long-lived and far more numerous than the short-lived osteoblasts and osteoclasts. Immured within the lacunar-canalicular system and mineralized matrix, osteocytes are ideally located throughout the bone to detect the need for, and accordingly choreograph, the bone regeneration process by independently controlling rate limiting steps of bone resorption and formation. Consistent with this role, emerging evidence indicates that signals arising from apoptotic and old/or dysfunctional osteocytes are seminal culprits in the pathogenesis of involutional, post-menopausal, steroid-, and immobilization-induced osteoporosis.

Optic disc assessment in the emergency department: a comparative study between the PanOptic and direct ophthalmoscopes.

Optic disc assessment is an essential part of the neurological examination of acutely unwell patients. This study compares the PanOptic ophthalmoscope with the direct ophthalmoscope for accuracy of diagnosis and ease of use. Patient satisfaction was also compared for the two instruments.

How common are palliative care needs among older people who die in the emergency department?

Objective: To determine the prevalence and nature of palliative care needs in people aged 65 years or more (65+) who die in emergency departments (EDs).

Methods: This was a retrospective analysis of routine hospital data from two EDs in South London. Patients aged 65+ living in the hospitals' catchment area who died in the ED during a 1 year period (2006-2007) were included.

How common are palliative care needs among older people who die in the emergency department?

Objective: To determine the prevalence and nature of palliative care needs in people aged 65 years or more (65+) who die in emergency departments (EDs).

Methods: This was a retrospective analysis of routine hospital data from two EDs in South London. Patients aged 65+ living in the hospitals' catchment area who died in the ED during a 1 year period (2006-2007) were included.

Individual care plans can reduce hospital admission rate for patients who frequently attend the emergency department.

Aim: To investigate the impact, in terms of hospital admission and investigations, of individual care plans for patients who frequently attend the emergency department (ED).

Method: 32 patients who regularly attended the ED at St Thomas' Hospital were included in the study. After review of ED and hospital case records, an individual care plan was prepared for future attendances.

What old means to bone.

The adverse effects of aging of other organs (ovaries at menopause) on the skeleton are well known, but ironically little is known of skeletal aging itself. Evidence indicates that age-related changes, such as oxidative stress, are fundamental mechanisms of the decline of bone mass and strength. Unlike the short-lived osteoclasts and osteoblasts, osteocytes--former osteoblasts entombed in the mineralized matrix--live as long as 50 years, and their death is dependent on skeletal age.

Dependence of bone yield (volume of bone formed per unit of cement surface area) on resorption cavity size during osteonal remodeling in human rib: implications for osteoblast function and the pathogenesis of age-related bone loss.

It is both a necessary and a sufficient condition for bone to be lost with age at any surface location that during remodeling the replacement of resorbed bone is incomplete. In both the ilium and the rib, the degree of such focal imbalance is smaller on the intracortical than on the endocortical or cancellous surfaces that are adjacent to bone marrow. The reason for this difference is unknown.

Trabecular packet-level lamellar density patterns differ by fracture status and bone formation rate in white females.

Spatial patterns of mineralization for human iliac crest cancellous bone were measured from images obtained by quantitative backscattered electron microscopy. Biopsies collected from vertebral fracture patients and healthy individuals with high or low bone formation rate (BFR(s)) were examined (fracture/low BFR(s): N=12, fracture/high BFR(s): N=10, normal/low BFR(s): N=12, normal/high BFR(s): N=15). 20 by 20 pixel square areas or smaller were sampled from superficial and deep remodeling packets.

Single injection digital anaesthesia: an easy technique for paediatric finger injuries.

The novel use of a single injection digital anaesthesia technique in children is described, which was found to be effective.

Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids.

Both aging and loss of sex steroids have adverse effects on skeletal homeostasis, but whether and how they may influence each others negative impact on bone remains unknown. We report herein that both female and male C57BL/6 mice progressively lost strength (as determined by load-to-failure measurements) and bone mineral density in the spine and femur between the ages of 4 and 31 months. These changes were temporally associated with decreased rate of remodeling as evidenced by decreased osteoblast and osteoclast numbers and decreased bone formation rate; as well as increased osteoblast and osteocyte apoptosis, increased reactive oxygen species levels, and decreased glutathione reductase activity and a corresponding increase in the phosphorylation of p53 and p66(shc), two key components of a signaling cascade that are activated by reactive oxygen species and influences apoptosis and lifespan.

Quantifying osteoblast and osteocyte apoptosis: challenges and rewards.

Since the initial demonstration of the phenomenon in murine and human bone sections approximately 10 yr ago, appreciation of the biologic significance of osteoblast apoptosis has contributed greatly not only to understanding the regulation of osteoblast number during physiologic bone remodeling, but also the pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs used for their treatment. It is now appreciated that all major regulators of bone metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and PTH-related protein (PTHrP), immobilization, and the oxidative stress associated with aging contribute to the regulation of osteoblast and osteocyte life span by modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important regulator of remodeling on the bone surface and a critical determinant of bone strength, independently of bone mass.

Independent and combined contributions of cancellous and cortical bone deficits to vertebral fracture risk in postmenopausal women.

Unlabelled: Using iliac bone histomorphometry on 78 patients with vertebral fracture and 66 healthy postmenopausal women, cortical thickness discriminated at least as well as any cancellous bone structural index between the two groups. Subjects with a deficit in both cortical and cancellous bone had much greater likelihood of fracture.

Introduction: Vertebral fracture is often attributed to disproportional loss of cancellous bone, but fracture patients may have deficits in cortical and cancellous bone.

Best evidence topic report. Cocaine induced myocardial ischaemia: nitrates versus benzodiazepines.

A short cut review was carried out to establish whether nitrates are better than benzodiazepines in the treatment of cocaine induced chest pain. Seven citations were reviewed of which two answered the three part question. The clinical bottom line is that in patients with cocaine induced chest pain it appears that nitrates or benzodiazepines are effective in combination or alone in resolving chest pain and improving cardiac performance.

Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss.

Unlabelled: Mechanical stimulation of cultured osteocytic cells attenuates their apoptosis. We report here that, conversely, reduced mechanical forces in the murine model of unloading by tail suspension increases the prevalence of osteocyte apoptosis, followed by bone resorption and loss of mineral and strength.

Introduction: Mechanical loading is critical for the maintenance of bone mass; weightlessness, as with reduced physical activity in old age, bed rest, or space flight, invariably leads to bone loss.

Does meta-chlorophenylpiperazine (mCPP) activate human platelets?

mCPP (meta-chlorophenylpiperazine), an agonist at serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 receptors, has been used as a probe of serotonergic function. We assessed its effect on platelet activation by measuring median platelet volume (MPV), the Sonoclot (SCT) pattern and plasma and intraplatelet serotonin. (a) In vitro study: MPV was measured (n = 7) using a high-resolution channelyzer: Saline (median and range (5.

Differences in osteocyte and lacunar density between Black and White American women.

We examined the differences in osteocyte and lacunar density between Black and White women, using previously obtained iliac bone biopsies from 34 healthy Black women, aged 21-70 years, and 94 White women, aged 20-73 years. For each subject, the density of osteocytes (Ot.N/B.

The morphological association between microcracks and osteocyte lacunae in human cortical bone.

We studied the spatial relationship between the osteocyte lacunar-canalicular network and microdamage accumulation in bone matrix. Rib sections from 9 white women aged 50-60 were stained with basic fuchsin and examined using bright-field and fluorescence microscopy. The results showed that the numerical and length density of cracks were 5-fold higher in interstitial bone than in osteons (P<0.

Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs.

Osteocytes, former osteoblasts entombed in the bone matrix, form an extensive cell communication network that is thought to detect microdamage and mechanical strains and to transmit signals leading to repair and compensatory bone augmentation or reduction. Bone active hormones and drugs control the integrity of this network by regulating osteocyte apoptosis, which might be a determinant of bone strength. Herein we demonstrate that mechanical stimulation by stretching activates the ERKs, which in turn are responsible for the attenuation of osteocyte apoptosis.