Measuring tissue water potential in marine macroalgae via an updated Chardakov method.

Regulation of tissue water potential is a key mechanism in macroalgal osmotic responses to changing external osmotic conditions, which are common in tidally influenced estuarine and intertidal systems. Nevertheless, significant knowledge gaps exist in our understanding of osmotic responses in macroalgae because few methods measure osmotic potential within macroalgal tissues. Leaf psychrometers have furthered understanding of osmotic potentials in terrestrial plant water relations, yet these have not been developed to measure the range of highly negative potential values found in marine macroalgae. To address these gaps, we present an effective, updated version of the Chardakov method to measure tissue water potential in macroalgae. Here, we present a case study examining macroalgal response in tissue water potential by two morphologically and evolutionarily distinct species, Ulva lactuca (Chlorophyta) and Hypnea musciformis (Rhodophyta) to four paired salinity and nutrient treatments at two temperatures. These treatments simulate a gradient from full coastal ocean conditions to brackish submarine groundwater discharge, an ecosystem type found on basaltic shorelines. Both algae demonstrated plasticity in osmotic response to submarine groundwater discharge with significant positive correlations between tissue water potential and proportion of submarine groundwater discharge in the treatment. These results are the first to describe macroalgal response in tissue water potential, a first step to understanding algal physiological ecology in such complex coastal environments. This revised Chardakov method is a valuable tool to better understand species-specific osmotic responses to ecologically relevant conditions, and can augment the study of other tidal systems and ontogenetic stages.

Patients not taking a previously prescribed bone active medication now prescribed medication through Ontario FLS.

In an Ontario fracture liaison service (FLS), we compared medication prescription rates among patients not taking a previously prescribed bone active medication to those with no previous prescription. Prescription rates were similar between these two groups of patients. The FLS provided a secondary opportunity for patients to initiate bone active medication. PURPOSE: We compared bone active medication prescription rates among patients presenting to an Ontario fracture liaison service (FLS) who reported not taking a previously prescribed bone active medication to those with no history of prescription. METHODS: Eligible patients were those screened in 39 fracture clinics between July 1, 2017, and September 15, 2019, who were not taking bone active medication at the time of screening and classified as high risk for future fracture based on CAROC or FRAX. Sociodemographic and clinical risk factor variables were assessed at screening. Bone active medication prescription rate was assessed within 6 months of screening and defined as having received a prescription for the medication from either a specialist or primary care provider. In cases where a specialist report was not available, patient self-reported data were collected. The chi-square test of independence was used to assess differences in prescription rates. RESULTS: Of 17,575 patients screened, eligible patients were 350 with a previous prescription and 2644 without a previous prescription. Compared with patients who reported no previous prescription, those who had a previous prescription were older, more likely to be female and to report a previous fracture, and less likely to smoke. There was no statistically significant difference between the medication prescription rate of patients with a previous prescription (73.7%) compared to patients with no previous prescription (70.7%) (p = 0.157). CONCLUSION: A large jurisdiction-wide FLS approach provided a secondary opportunity to patients who were not taking a previously prescribed bone active medication to initiate that medication.

Fragility fracture patients with a history of prior fractures more likely to present with multiple risk factors: findings from a province-wide fracture liaison service.

We examined the demographic characteristics and risk factors of FLS fragility fracture patients who had sustained prior fragility fracture(s) and found that this is an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle. PURPOSE: Our primary objective was to examine whether fragility fracture patients presenting to a provincial fracture liaison service (FLS) having a history of prior fractures, versus those without, differ in demographic characteristics and risk factors for future fracture. A secondary objective was to understand if those who report two or more prior fractures differ from those reporting one prior fracture. METHODS: This cohort study included fragility fracture patients aged 50 + enrolled in the Ontario FLS between July 2017 and September 2019. Patients with versus those without prior fractures were compared on age, sex, index fracture site, biological parents' history of hip fracture, current fracture due to a fall, history of feeling unsteady when walking, history of falls in the past year, smoking, oral steroid use, and comorbid chronic conditions. Pearson's chi-square, Fischer's exact, and analysis of variance tests were used to assess differences. RESULTS: Among 14,454 patients, 16.8% (n = 2428) reported a history of one or more prior fractures after the age of 40. They were significantly more likely to be older, female, with a higher number of comorbidities, with greater incidence of falls, and feel unsteady when walking. Compared to those with one prior fracture, patients with greater than one prior fracture were more likely to report falls in the past year and feel unsteady when walking. CONCLUSION: Findings suggest that FLS fragility fracture patients who had sustained prior fragility fracture are an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle.

Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture.

PURPOSE: This work investigated the endocytic pathways taken by poly(isobutylcyanoacrylate) (PIBCA) nanoparticles differing in their surface composition and architecture, assuming that this might determine their efficiency of intracellular drug delivery. METHODS: Nanoparticles (A0, A25, A100, R0, R25 ) were prepared by anionic or redox radical emulsion polymerization using mixtures of dextran and fucoidan (0, 25, 100 % in fucoidan). Cell uptake was evaluated by incubating J774A.1 macrophages with nanoparticles. Endocytic pathways were studied by incubating cells with endocytic pathway inhibitors (chlorpromazine, genistein, cytochalasin D, methyl-ß-cyclodextrin and nocodazole) and nanoparticle uptake was evaluated by flow cytometry and confocal microscopy. RESULTS: The fucoidan-coated PIBCA nanoparticles A25 were internalized 3-fold more efficiently than R25 due to the different architecture of the fucoidan chains presented on the surface. Different fucoidan density and architecture led to different internalization pathway preferred by the cells. Large A100 nanoparticles with surface was covered with fucoidan chains in a loop and train configuration were internalized the most efficiently, 47-fold compared with A0, and 3-fold compared with R0 and R25 through non-endocytic energy-independent pathways and reached the cell cytoplasm. CONCLUSION: Internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. In turn, this influenced the extent of internalization and localization of accumulated nanoparticles within cells. The results are of interest for rationalizing the design of nanoparticles for potential cytoplamic drug delivery by controlling the nature of the nanoparticle surface.

Patients 80 + have similar medication initiation rates to those aged 50-79 in Ontario FLS.

Among individuals presenting to an Ontario FLS, we compared bone active medication initiation rates of patients 80 years and older with those 50-79 years old. After accounting for fracture risk status, there was no statistically significant difference in medication initiation rates between the two age groups INTRODUCTION: A Fracture Liaison Service (FLS) offers post-fracture services to individuals over the age of 50 years and could potentially address age inequities in pharmacotherapy often observed for older adults. Among individuals presenting to an Ontario FLS and classified as being at high risk for future fracture, our objective was to compare bone active medication initiation rates of patients 80 years and older with those 50-79 years old. METHODS: In 39 FLS fracture clinics across Ontario, Canada, fracture prevention coordinators identified, assessed, and facilitated the referral of eligible patients for bone densitometry, fracture risk assessment, and implementation of pharmacotherapy in patients classified as high risk for future fracture. Variables assessed at baseline included age, sex, marital status, living location, fracture location, history of previous fracture, parent's history of hip fracture, history of falls, and fracture risk status. At 6 months, bone active medication initiation was assessed in patients classified as high risk for future fracture. The Chi-square test of independence was used to compare medication initiation rates between patients 80 + and those 50-79 years old. RESULTS: Our sample size consisted of 808 patients aged 50-79 years and 346 aged 80 + years. After accounting for fracture risk status, there was no statistically significant difference in medication initiation rates of patients 50-79 and 80 + years old (76.9% versus 73.7%, p = 0.251). CONCLUSION: A systematic approach to identifying patients at high risk for future fracture and tailoring treatment recommendations to these patients appeared to eliminate differences in treatment initiation rates based on older age.

Few fragility fracture patients perceive that their bone health is affected by their comorbidities and medications.

We examined fragility fracture patients' perceptions of associations between bone health and other chronic conditions and medications. Awareness of the associations between bone health and these conditions and medications was low. Providers should increase patients' awareness of these associations in order to minimize the risk of future fracture. INTRODUCTION: Among patients with a fragility fracture presenting with at least one other chronic health condition, we examined (1) perceptions of the association between bone health and their other health conditions, and (2) perceptions of the association between bone health and prescribed medications taken for other health conditions. METHODS: We identified fragility fracture patients presenting to a Canadian urban fracture clinic with at least one self-reported chronic health condition (in addition to bone fragility). In-depth interviews, 60-90 min in duration, were conducted. Our qualitative methodology was informed by saliency analysis. RESULTS: We interviewed 26 patients (21 females, 5 males) aged 45 to 84 years old. Participants were taking 1-13 medications each and presented with a variety of comorbidities (range 1-7). All participants described at least one condition or medication they were currently taking for which there existed evidence of a negative effect on bone health (increased risk of fracture, bone loss, falling). Two participants perceived a correct association between their other health conditions and compromised bone health, and four participants perceived a correct association between their medications and compromised bone health. CONCLUSION: All patients reported a chronic health condition and/or were taking at least one medication that potentially compromised their bone health. Patient awareness of the association between bone health and other health conditions and prescribed medications was low. Health care providers should increase patients' awareness of the bone health significance of their chronic conditions and medications in order to minimize the risk of future fracture.

Changes in laboratory markers of thrombotic risk early in the first trimester of pregnancy may be linked to an increase in estradiol and progesterone.

BACKGROUND: Pregnant women are at increased risk of venous thrombosis compared to non-pregnant women. Epidemiological and laboratory data suggest that hypercoagulability begins in the first trimester but it is unknown exactly how early in pregnancy this develops. The mechanisms that result in a prothrombotic state may involve oestrogens and progestogens. METHODS: Plasma samples were taken prior to conception and five times in early pregnancy, up to Day 59 gestation, from 22 women undergoing natural cycle in vitro fertilization, who subsequently gave birth at term following a normal pregnancy. Thrombin generation, free Protein S, Ddimer, Fibrinogen, factor VIII, estradiol and progesterone were measured. To counter inter-individual variability, the change in laboratory measurements between the pre-pregnant and pregnant state were measured over time. RESULTS: Peak thrombin, Endogenous Thrombin Potential, Velocity Index and fibrinogen significantly increased, and free Protein S significantly decreased, from pre-pregnancy levels, by 32 days gestation. Ddimer and VIII significantly increased from pre-pregnancy levels by 59 days gestation. Estradiol significantly increased by Day 32 gestation with a non-significant increase of 67% by Day 24 gestation. Progesterone significantly increased by Day 32 gestation. Almost all laboratory markers of thrombosis correlated significantly with estradiol and progesterone. CONCLUSION: Our work is the first to demonstrate that the prothrombotic state develops very early in the first trimester. Laboratory markers of hypercoagulability correlate significantly with estradiol and progesterone suggesting these are linked to the prothrombotic state of pregnancy. Clinicians should consider commencing thromboprophylaxis early in the first trimester in women at high thrombotic risk.

Being the 'med reg': an exploration of junior doctors' perceptions of the medical registrar role.

The role of the medical registrar is challenging and acknowledged as being a disincentive to a career in medicine for some junior doctors. We set out to build a broader understanding of the role through exploration of Foundation Doctors' and Core Medical Trainees' perceptions of the role. Data, gathered from focus groups, were analysed using a framework approach. Six key themes were identified, which were grouped under the headings 'perceptions of the medical registrar role' and 'transition into the role'. Our work builds on existing literature to inform a deeper understanding of how junior doctors perceive the medical registrar role. In light of our findings we offer suggestions on possible training initiatives to tackle the issues identified. We also highlight positive perceptions of the role and emphasise the key ambassadorial role that current medical registrars have in relation to attracting tomorrow's medical registrars to the specialty.

ß-cell specific T-lymphocyte response has a distinct inflammatory phenotype in children with Type 1 diabetes compared with adults.

AIM: To examine the hypothesis that the quality, magnitude and breadth of helper T-lymphocyte responses to ß cells differ in Type 1 diabetes according to diagnosis in childhood or adulthood. METHODS: We studied helper T-lymphocyte reactivity against ß-cell autoantigens by measuring production of the pro-inflammatory cytokine interferon-γ and the anti-inflammatory cytokine interleukin-10, using enzyme-linked immunospot assays in 61 people with Type 1 diabetes (within 3 months of diagnosis, positive for HLA DRB1*0301 and/or *0401), of whom 33 were children/adolescents, and a further 91 were unaffected siblings. RESULTS: Interferon-γ responses were significantly more frequent in children with Type 1 diabetes compared with adults (85 vs 61%; P = 0.04). Insulin and proinsulin peptides were preferentially targeted in children (P = 0.0001 and P = 0.04, respectively) and the breadth of the interferon-γ response was also greater, with 70% of children having an interferon-γ response to three or more peptides compared with 14% of adults (P < 0.0001). Islet ß-cell antigen-specific interleukin-10 responses were similar in children and adults in terms of frequency, breadth and magnitude, with the exception of responses to glutamic acid decarboxylase 65, which were significantly less frequent in adults. CONCLUSIONS: At diagnosis of Type 1 diabetes, pro-inflammatory autoreactivity is significantly more prevalent, focuses on a wider range of targets, and is more focused on insulin/proinsulin in children than adults. We interpret this as indicating a more aggressive immunological response in the younger age group that is especially characterized by loss of tolerance to proinsulin. These findings highlight the existence of age-related heterogeneity in Type 1 diabetes pathogenesis that could have relevance to the development of immune-based therapies.

Patients do not have a consistent understanding of high risk for future fracture: a qualitative study of patients from a post-fracture secondary prevention program.

UNLABELLED: We examined fracture patients' understanding of "high" fracture risk after they were screened through a post-fracture secondary prevention program and educated about their risk verbally, numerically, and graphically. Our findings suggest that messages about fracture risk are confusing to patients and need to be modified to better suit patients' needs. INTRODUCTION: The aim of this study was to examine fracture patients' understanding of high risk for future fracture. METHODS: We conducted an in-depth qualitative study in patients who were high risk for future fracture. Patients were screened through the Osteoporosis Exemplary Care Program where they were educated about fracture risk: verbally told they were "high risk" for future fracture, given a numerical prompt that they had a >20 % chance of future fracture over the next 10 years, and given a visual graph highlighting the "high risk" segment. This information about fracture risk was also relayed to patients' primary care physicians (PCPs) and specialists. Participants were interviewed at baseline (within six months of fracture) and follow-up (after visit with a PCP and/or specialist) and asked to recall their understanding of risk and whether it applied to them. RESULTS: We recruited 27 patients (20 females, 7 males) aged 51-87 years old. Fractures were sustained at the wrist (n = 7), hip (n = 7), vertebrae (n = 2), and multiple or other locations (n = 11). While most participants recalled they had been labeled as "high risk" (verbal cue), most were unable to correctly recall the other elements of risk (numerical, graphical). Further, approximately half of the patients who recalled they were high risk did not believe that high risk applied, or had meaning, to them. Participants also had difficulty explaining what they were at risk for. CONCLUSIONS: Our results suggest that health care providers' messages about fracture risk are confusing to patients and that these messages need to be modified to better suit patients' needs.

Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model.

Peptide immunotherapy (PIT) is a targeted therapeutic approach, involving administration of disease-associated peptides, with the aim of restoring antigen-specific immunological tolerance without generalized immunosuppression. In type 1 diabetes, proinsulin is a primary antigen targeted by the autoimmune response, and is therefore a strong candidate for exploitation via PIT in this setting. To elucidate the optimal conditions for proinsulin-based PIT and explore mechanisms of action, we developed a preclinical model of proinsulin autoimmunity in a humanized HLA-DRB1*0401 transgenic HLA-DR4 Tg mouse. Once proinsulin-specific tolerance is broken, HLA-DR4 Tg mice develop autoinflammatory responses, including proinsulin-specific T cell proliferation, interferon (IFN)-γ and autoantibody production. These are preventable and quenchable by pre- and post-induction treatment, respectively, using intradermal proinsulin-PIT injections. Intradermal proinsulin-PIT enhances proliferation of regulatory [forkhead box protein 3 (FoxP3(+))CD25(high) ] CD4 T cells, including those capable of proinsulin-specific regulation, suggesting this as its main mode of action. In contrast, peptide delivered intradermally on the surface of vitamin D3-modulated (tolerogenic) dendritic cells, controls autoimmunity in association with proinsulin-specific IL-10 production, but no change in regulatory CD4 T cells. These studies define a humanized, translational model for in vivo optimization of PIT to control autoimmunity in type 1 diabetes and indicate that dominant mechanisms of action differ according to mode of peptide delivery.

Non-pharmacological strategies used by patients at high risk for future fracture to manage fracture risk--a qualitative study.

UNLABELLED: We examined patients' self-management of bone health and fracture risk, particularly behaviors other than medication use and seeking diagnostic testing. Awareness of fracture risk was accompanied by positive lifestyle changes in participants' lives such as being careful. Future research should evaluate how lifestyle changes mitigate fracture risk. INTRODUCTION: We examined patients' understanding of bone health and self-management decisions regarding bone health and fracture risk, particularly behaviors other than medication use and seeking diagnostic testing. METHODS: A phenomenological (qualitative) study was conducted. English-speaking patients, 65+ years old, who were "high risk" for future fracture and prescribed pharmacotherapy after being screened through a post-fracture osteoporosis initiative were eligible. Patients were interviewed for 1-2 h and were asked to discuss perceptions of bone health status (bone densitometry results and perceived fracture risk), recommendations received for bone health, and lifestyle changes since their most recent fracture. We analyzed the data guided by Giorgi's methodology. RESULTS: We interviewed 21 fracture patients (6 males and 15 females), aged 65 to 88 years old. With the exception of one participant, all participants appeared to understand that they had low bone mass and were at risk of sustaining another fracture. Most participants (n = 20) were predominantly concerned about being careful, and they focused their responses on personal and environmental factors that they perceived to be modifiable. Participants also spoke about strategies to manage their bone health such as exercise, having a healthy diet and taking supplements, and using aids and devices. Non-pharmacological strategies used by patients appeared to be independent of current use of pharmacotherapy. CONCLUSIONS: Awareness of fracture risk was accompanied by a number of positive lifestyle changes in participants' lives such as being careful and engaging in exercise. Future research needs to evaluate how lifestyle changes such as being careful mitigate fracture risk.

Performance of the LHCb RICH detector at the LHC.

The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This provides charged particle identification over a wide momentum range, from 2-100 GeV/c. The operation and control, software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types (π, K, p) is achieved.

Patients reject the concept of fragility fracture--a new understanding based on fracture patients' communication.

UNLABELLED: We examined patients' communication about fragility fractures to gain insight into why patients do not connect fractures to bone health. The term "fragility" fracture was a misnomer to patients who perceived the event as physically and emotionally traumatic. Improved communication about such fractures could facilitate awareness of bone health. INTRODUCTION: We examined patients' communication about fragility fractures to gain insight into why patients do not perceive the connection between their fracture and low bone mass. METHODS: A descriptive phenomenological (qualitative) study was conducted. During face-to-face interviews, the participants described the experience of their fracture in detail and the circumstances surrounding the fracture. Data analysis was guided by Giorgi's methodology. English-speaking male and female patients aged 65+ years and "high" risk for future fracture were eligible and screened for osteoporosis through an established screening program at an urban teaching hospital. RESULTS: We recruited 30 participants (9 males, 21 females), aged 65-88, who presented with a hip (n = 11), wrist (n = 11), shoulder (n = 6), or other (n = 2) fracture. Ten of the 30 fractures occurred inside the home and the remaining fractures occurred outside the home. Sustaining a fragility fracture was perceived as a traumatic event, both physically and emotionally. In general, participants used forceful, action-oriented words and referred to hard surfaces to describe the experience. Explanations for the fracture, other than bone quality, were often reported, especially that falls were "freak" or "fluke" events. Patients who sustained a fracture under more mundane circumstances seemed more likely to perceive a connection between the fracture and their bone health. CONCLUSIONS: The term fragility fracture was a misnomer for many older adults. By reexamining how this term is communicated to fracture patients, health care providers may better facilitate patients' awareness of bone health.

Systematic review on interventions to improve osteoporosis investigation and treatment in fragility fracture patients.

This study aims to determine osteoporosis (OP) investigation and treatment within post-fracture initiatives conducted in fracture clinics and other orthopedic environments. A systematic review was conducted. Eligibility criteria were: hip fracture patients plus all other fracture patients presenting with a fragility fracture, orthopedic setting where orthopedic physicians/staff were involved, intervention to improve OP management, primary data on ≥20 patients from randomized controlled trials (RCTs) and other study designs. We calculated outcome data within 6 months of screening from an intention-to-treat principle to derive an equated proportion (EP) across interventions. Outcomes were: (1) proportion of patients investigated with bone densitometry, (2) proportion of patients initiating OP medication, and (3) proportion of patients taking OP medication. We identified 2,259 citations, of which 57 articles that included 64 intervention groups were eligible. The median EP for patients investigated was 43% and the 75th percentile was 71%. The median EP for medication initiation was 22% and the 75th percentile was 34%. The median EP for medication taking was 27.5% and the 75th percentile was 43%. The EPs for all outcomes were higher for interventions with dedicated personnel to implement the intervention and those within which bone mineral density testing and/or treatment were included. In studies with an EP, up to 71% of patients were investigated for OP, but <35% initiated medication, and <45% were taking medication within 6 months of screening. Calculating an EP allowed us to compare outcomes across the studies, therefore capturing both RCTs and other study designs typical of real-world settings.

An investigation of the impact of the location and timing of antigen-specific T cell division on airways inflammation.

It is widely accepted that allergic asthma is orchestrated by T helper type 2 lymphocytes specific for inhaled allergen. However, it remains unclear where and when T cell activation and division occurs after allergen challenge, and whether these factors have a significant impact on airways inflammation. We therefore employed a CD4-T cell receptor transgenic adoptive transfer model in conjunction with laser scanning cytometry to characterize the location and timing of T cell division in asthma in vivo. Thus, for the first time we have directly assessed the division of antigen-specific T cells in situ. We found that accumulation of divided antigen-specific T cells in the lungs appeared to occur in two waves. The first very early wave was apparent before dividing T cells could be detected in the lymph node (LN) and coincided with neutrophil influx. The second wave of divided T cells accumulating in lung followed the appearance of these cells in LN and coincided with peak eosinophilia. Furthermore, accumulation of antigen-specific T cells in the draining LN and lung tissue, together with accompanying pathology, was reduced by intervention with the sphingosine 1-phosphate receptor agonist FTY720 2 days after challenge. These findings provide greater insight into the timing and location of antigen-specific T cell division in airways inflammation, indicate that distinct phases and locations of antigen presentation may be associated with different aspects of pathology and that therapeutics targeted against leukocyte migration may be useful in these conditions.

A program with a dedicated coordinator improved chart documentation of osteoporosis after fragility fracture.

UNLABELLED: Post-fracture osteoporosis care is becoming recognized as essential by the orthopaedic community, but programs and systems are needed to ensure that this care is routinely provided. Chart documentation related to OP, which is valuable for continuity of care, increased significantly following establishment of an osteoporosis program with a dedicated coordinator. INTRODUCTION: Post-fracture osteoporosis (OP) care has been repeatedly reported to be inadequate. Through a coordinator-based program, we addressed OP care for more than 95% of fragility fracture patients (1), but we do not know if documentation by orthopaedic surgeons improved. The literature suggests that chart documentation, though underestimating true care, is an indicator of the salient aspects of a condition. Thus chart documentation could be used to reflect an emerging recognition of OP as an important issue to be addressed in the orthopaedic management of the fragility fracture. The purpose of this study was to evaluate if there was an increased documentation of OP by orthopaedic surgeons before and after introduction of a coordinator-based program where the coordinator was known to address OP in 95% of cases. METHODS: Chart audits were conducted to quantify OP documentation for patients treated after program initiation compared with age-, sex-, and fracture type-matched controls who presented prior to program implementation. Documentation rates were compared using chi(2) tests. Multivariable logistic regression analyses were performed to identify patient characteristics associated with OP-related documentation. RESULTS: After program implementation, chart documentation of OP diagnosis (unadjusted OR 2.2, 95% CI 1.1-4.4), of referral for OP follow-up (unadjusted OR 3.1, 95% CI 1.5-6.1), and of initiation of OP management (unadjusted OR 8.2, 95% CI 4.0-16.5) by orthopaedic surgeons was more likely. Being in the post-implementation group was stronger than any patient factors in predicting OP charting. CONCLUSIONS: Physicians working in a clinic with a coordinator-based OP program were more likely to document OP-related care in patients' medical charts. We believe this in turn reflected increased attention to OP by physicians in the orthopaedic management of fragility fractures.

Osteonal effects on elastic modulus and fatigue life in equine bone.

We hypothesized that recently formed, incompletely mineralized, and thus, relatively deformable osteons in the equine third metacarpus enhance in vitro load-controlled fatigue life in two ways. Macroscopically, there is a compliance effect, because reduced tissue elastic modulus diminishes the stress required to reach a given strain. Microscopically, there is a cement line effect, in which new osteons and their cement lines more effectively serve as barriers to crack propagation. We studied 18 4 x 10 x 100 mm beams from the medial, lateral, and dorsal cortices of metacarpal bones from 6 thoroughbred racehorses. Following load-controlled fatigue testing to fracture in 4 point bending, a transverse, 100 microm thick, basic fuchsin-stained cross-section was taken from the load-bearing region. The number and diameter of all intact (and thus recently formed/compliant) secondary osteons in a 3.8 x 3.8 mm region in the center of the section were determined. The associated area fraction and cement line length of intact osteons were calculated, and the relationships between these variables, elastic modulus (E), and the logarithm of fatigue life (logN(F)) were analyzed. As expected, logN(F) was negatively correlated with E, which was in turn negatively correlated with intact osteon area fraction and density. (LogN(F))/E increased in proportion to intact osteon density and nonlinearly with cement line density (mm/mm(2)). These results support the hypothesis that remodeling extends load-controlled fatigue life both through the creation of osteonal barriers to microdamage propagation and modulus reduction.

Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: a systematic review.

Fragility fractures are a strong indicator of underlying osteoporosis (OP). With the risk of future fracture being increased 1.5- to 9.5-fold following a fragility fracture, the diagnosis and treatment of OP in men and women with fragility fractures provides the opportunity to prevent future fragility fractures. This review describes the current status of practice in investigation and diagnosis of OP in men and women with fragility fractures, the rates and types of postfracture treatment in patients with fragility fractures and OP, interventions undertaken in this population, and the barriers to OP identification and treatment. A literature search performed in Medline, Healthstar, CINAHL, EMBASE, PreMedline, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 37 studies on OP diagnosis, treatment, and interventions. The studies varied in design methodology, study facilities, types of fractures, and pharmacological treatments. Some studies revealed that no patients with fragility fractures received investigation or treatment for underlying OP. Investigation of OP by bone mineral density was low: 14 of 16 studies reported investigation of less than 32% of patients. Investigation by bone mineral density resulted in high rates of OP diagnosis (35-100%), but only moderate use of calcium and vitamin D (8-62%, median 18%) and bisphosphates (0.5-38%) in patients investigated postfracture. Studies on barriers to OP identification and treatment focused on various groups of health practitioners. Barriers included the cost of therapies, time and cost of resources for diagnosis, concerns about medications, and the lack of clarity regarding the responsibility to undertake this care.

Yellow fever oubreak southern sudan; 2003

In May 2003; an outbreak of fatal hemorrhagic fever; caused by yellow fever virus; occurred in southern Sudan. Phylogenetic analysis showed that the virus belonged to the East African genotype; which supports the contention that yellow fever is endemic in East Africa with the potential to cause large outbreaks in humans. number of the residents moved back to the Imatong region. During April and May 2003 suspected cases of hemorrhagic illness were reported; and blood samples collected from Sarianga; Itohom; enyleny; Tarafafa; Lofi; and Locomo villages were tested at the Kenya Medical Research