Development, implementation and evaluation of a multinational FLS mentorship programme in Latin America.

Realising the benefits of systematic secondary fracture prevention requires supporting local sites to get started and becoming effective. We here describe the development, implementation and impact of a regional fracture liaison service (FLS) mentorship programme in Latin America that led to 64 FLS getting started and coverage of 17,205 patients. INTRODUCTION: Despite treatments and service models to deliver effective secondary fracture prevention, most patients are left untreated after a fragility fracture. To improve the capability to get FLS started and more effective, we describe the development, implementation and evaluation of an international programme to develop national communities of FLS mentors as part of the Capture the Fracture Partnership in Latin America. METHODS: The IOF regional team and the University of Oxford developed the curriculum and associated resources for training mentors in setting up FLS, service improvement and mentorship. Mentors were selected during a preparatory meeting, trained using live online sessions followed by regular mentor-led post-training meetings. The programme was evaluated using a pre-training needs assessment and post-training evaluation based on Moore's outcomes. RESULTS: The mentorship programme was initiated in Mexico, Brazil, Colombia and Argentina. The mentors were multidisciplinary, including orthopaedic surgery, rehabilitation, rheumatology, endocrinology, geriatrics, gynaecology and internal medicine. There was 100% participation in training sessions and reported satisfaction with the training. Since the initiation of the training programme, 22 FLS have been set up in Mexico, 30 in Brazil, 3 in Colombia and 9 in Argentina, in comparison with two in Chile and none in any other LATAM countries that were not involved in the mentorship programme. This equates to approximately 17,025 additional patients identified from 2019 to 2021 after initiation of mentorship. The mentors have engaged with 58 FLS for service development. Post-training activities include two published national best practice guidelines and other country-specific resources for FLS in the local language. CONCLUSION: Despite the COVID pandemic, the mentorship pillar of the Capture the Fracture Partnership has developed a community of FLS mentors with measurable improvement in national FLS provision. The programme is a potentially scalable platform to develop communities of mentors in other countries.

Voriconazole-induced periostitis.

Voriconazole is a fluorinated drug from the triazole group that is widely used in the prophylaxis and treatment of fungal infections in immunosuppressed patients. Chronic use of this medication can generate, as an adverse effect, a multifocal, asymmetric, diffuse and nodular periosteal reaction, associated with severe and disabling skeletal pain and elevated alkaline phosphatase and serum fluoride. Radiography is the imaging technique of choice for periostitis diagnosis. In general, clinical manifestations and radiographic findings disappear, when the drug is discontinued. We report the clinical case of a 44 year-old woman diagnosed with acute myeloid leukemia, who developed an invasive fungal infection treated with voriconazole after a stem cell transplant. Nine months after starting antifungal treatment, she manifested symptoms and radiological signs compatible with periostitis. Due to clinical suspicion, we decided to suspend voriconazole, with consequent resolution of clinical manifestations and radiological findings.

High-fidelity simulation for continuing education in nurse anesthesia.

Simulation represents a true paradigm shift in teaching and learning that has revolutionized healthcare education. However, few continuing education opportunities for anesthesia providers exist using simulation of any type. This article explores the usefulness of high-fidelity simulation (HFS) as a valuable tool for continuing education and reports the results of a needs assessment conducted among 22 practicing nurse anesthetists. The questions related to their exposure to HFS and asked them to rank their experience with 11 anesthesia events. Next, respondents were asked to rank a similar list of anesthesia events that would be useful for continuing education using simulation. Of participants, 71% ranked advanced cardiac life support scenarios, anesthesia machine mishaps, and malignant hyperthermia as highly effective choices for using HFS. Eighty-one percent of participants identified that they envision simulation as a valuable tool to assess competency, but respondents had mixed written responses when asked if simulation should be used for recertification. This needs assessment represents a beginning, grassroots attempt to establish nurse anesthetists' perceptions related to using HFS as a tool for continuing education.

A late Eemian aridity pulse in central Europe during the last glacial inception.

Investigating the processes that led to the end of the last interglacial period is relevant for understanding how our ongoing interglacial will end, which has been a matter of much debate (see, for example, refs 1, 2). A recent ice core from Greenland demonstrates climate cooling from 122,000 years ago driven by orbitally controlled insolation, with glacial inception at 118,000 years ago. Here we present an annually resolved, layer-counted record of varve thickness, quartz grain size and pollen assemblages from a maar lake in the Eifel (Germany), which documents a late Eemian aridity pulse lasting 468 years with dust storms, aridity, bushfire and a decline of thermophilous trees at the time of glacial inception. We interpret the decrease in both precipitation and temperature as an indication of a close link of this extreme climate event to a sudden southward shift of the position of the North Atlantic drift, the ocean current that brings warm surface waters to the northern European region. The late Eemian aridity pulse occurred at a 65 degrees N July insolation of 416 W m(-2), close to today's value of 428 W m(-2) (ref. 9), and may therefore be relevant for the interpretation of present-day climate variability.

Transfusion in the critically ill: does it affect outcome?

Anemia and red blood cell (RBC) transfusions are common in critically ill and injured, trauma, and surgical patients. Tolerance of anemia is highly variable, depending on the presence of cardiovascular and other comorbid diseases that may diminish the hemodynamic response to a lower hemoglobin (Hb) level. The quest to define a minimum threshold Hb concentration at which patients achieve significant benefit to improve outcome has not yet been identified. Complications related to RBC transfusion are related to RBC storage and intrinsic properties of donor allogeneic RBCs, including bacterial contamination, transfusion-related acute lung injury, and transfusion-related immunomodulation. The best evidence related to transfusion-related outcome involves titrating transfusion requirements to parameters of severity of illness rather than arbitrarily defined Hb levels.

Emerging issues for the postbariatric surgical patient.

Millions of individuals in the United States and around the world are overweight or obese. Bariatric surgery is now considered an evidenced-based choice for sustainable long-term weight loss and may reduce obesity-related comorbidities such as diabetes and obstructive sleep apnea. As bariatric surgical procedures increase, it can be expected that intensive care unit (ICU) admissions will increase as well. An emerging ICU population includes postbariatric patients either immediately after undergoing bariatric surgery or returning for subsequent surgical procedures. Massive weight loss following surgery leads to an excess of lax, overstretched skin, causing physical discomfort and psychosocial problems. It is important to understand the complex pathophysiological changes that occur in order to care for this growing population of patients. This review addresses the growing and evolving issues related to the complex nature of the postbariatric ICU patients.

The influence of gaze stabilization and fixation on stepping reactions in younger and older adults.

PURPOSE: To date, there has been little evidence to suggest the importance of foveal viewing versus peripheral retina viewing when trying to recover from a perturbation. The purposes of this investigation were to (1) determine whether a visual target can be stabilized on the fovea during a perturbation, (2) determine whether stepping responses following a perturbation are influenced by foveal fixation, and (3) compare gaze stability and stepping responses between young and aging adults. MATERIALS/METHODS: Ten young adults and 10 aging adults were asked to wear an eye-tracking device linked to a kinematic tracking system during perturbations. Perturbations were delivered under 2 conditions: control (no instructions regarding gaze location were given) and earth-fixed (EF) (subjects were asked to fixate gaze on an EF target). Stepping responses were recorded via force plates. Gaze stability, reported as percent foveal fixation (% FF), was calculated from eye-tracking data. Step latencies (SLs) were computed from force plate data. A 2 x 2 analysis of variance was used to assess statistical significance between groups. For the young and aging adults, linear correlations were made to identify relationships between % FF and SL. RESULTS: For each condition, aging adults took longer to initiate a step (control, P = .002; EF, P = .003). Young adults were better at maintaining gaze fixation than older adults (P = .0045). Linear correlations demonstrated significant negative relationships between SL and % FF for young (r = -0.76, P = .001) and older (r = -0.87, P = .0001) adults. As % FF increased, SL decreased. CONCLUSIONS: The ability to maintain gaze fixation of an EF target may be important in reducing SL following a perturbation. Older adult subjects demonstrated a decreased ability to fixate a target during balance tasks while also displaying longer SLs.

Nonclassical HLA-G molecules are classical peptide presenters.

BACKGROUND: The physiological functions of the classical HLA (human leukocyte antigen) molecules, HLA-A, HLA-B and HLA-C, are to present peptides to T cells and to inhibit the activity of natural killer cells. In contrast, the functions of nonclassical HLA-molecules, such as HLA-E, HLA-F and HLA-G, remain to be established. The expression of HLA-G is largely limited to the placental trophoblast, where it might mediate protection of the fetus from rejection by the mother. Achieving the aim of understanding the function of HLA-G should be facilitated by information on the biochemical properties of HLA-G molecules, especially on their potential ability to act as peptide receptors. RESULTS: To study peptide presentation by HLA-G, we used stably transfected LCL721.221 cells as a source of HLA-G molecules and analysed the spectrum of extracted peptides by individual and pool sequencing. Our results indicate that HLA-G molecules, like classical HLA molecules, are associated with a wide array of peptides derived from cellular proteins. Peptides presented by HLA-G usually consisted of 9 amino acids, and adhered to a specific sequence motif, with anchor residues at position 2 (isoleucine or leucine), position 3 (proline) and the carboxy-terminal position 9 (leucine). Thus, the HLA-G peptide ligand motif follows the principles of classical HLA motifs, although it displays its own unique features. Peptide-binding assays indicated that two of the three anchor residues were sufficient for binding, and that the three natural HLA-G ligands that we identified bound, not only to HLA-G, but also to HLA-A2. This was not surprising, because the binding pockets of HLA-A2 and HLA-G overlap in their ability to recognize anchor residues at positions 2 and 9. Likewise, some, but not all, HLA-A2 peptide ligands could also bind to HLA-G. CONCLUSIONS: Nonclassical HLA-G molecules present peptides essentially in the same way as classical HLA molecules do. We determined the peptide motif that is specifically recognized by HLA-G; its basic features are described by the sequence XI/LPXXXXXL: This information should help to elucidate the physiological role of HLA-G molecules at the fetal-maternal interface. Most likely, this role is to protect fetal cells from lysis by natural killer cells, and possibly to present foreign peptides to a class of T cells that has not yet been identified.

Increased FDG bone marrow uptake after intracoronary progenitor cell therapy.

UNLABELLED: Patients with coronary artery disease who undergo FDG, PET for therapy monitoring after intracoronary progenitor cell infusion (PCT) show an increased bone marrow uptake in some cases. AIM of the study was to evaluate the systemic bone marrow glucose metabolism in this patient group after PCT. PATIENTS, METHODS: FDG bone marrow uptake (BMU), measured as standardized uptake value (SUVmax) in the thoracic spine, was retrospectively evaluated in 23 control patients who did not receive PCT and in 75 patients who received PCT 3 +/- 2.2 days before PET scanning. Five out of them were pretreated with granulocyte colony-stimulating factor (G-CSF) 5 days prior to PCT and 10 +/- 1.2 days before PET scanning. In 39 patients who received only PCT without G-CSF and underwent PET therapy monitoring 4 months later, baseline and follow up bone marrow uptake were measured. Leucocytes, C-reactive protein (CRP) levels and the influence of nicotine consumption were compared with the BMU. RESULTS: In patients (n = 70) who received PCT without G-CSF, BMU median (1.3) was slightly, but significantly higher than in the controls (1.0) (p = 0.02) regardless nicotine consumption. BMU did not change significantly 4 months later (1.2) (p = 0.41, n.s.). After G-CSF pretreatment, patients showed a significantly higher bone marrow uptake (3.7) compared to patients only treated with PCT (1.3) (p = 0.023). Leucocyte blood levels were significantly higher in patients with a BMU > or =2.5 compared to patients with a bone marrow SUVmax <2.5 (p<0.001). CRP values did not correlate with the BMU (rho -0.02, p = 0.38). CONCLUSION: Monitoring PCT patients, a slightly increased FDG BMU may be observed which remains unchanged for several months. Unspecific bone marrow reactions after PCT may be associated with increased leucocyte blood levels and play a role in the changed systemic glucose BMU. In addition, pretreatment with G-CSF shows an intense amplification of BMU.

Spiral Salmonella assay: validation against the standard pour-plate assay.

The spiral Ames assay, an automated approach to bacterial mutagenicity testing which simplifies the test procedure and reduces the amount of drug required to generate mutagenic dose-response information, has been evaluated and validated for routine screening. The spiral plater delivers the Salmonella bacteria, exogenous metabolic activation system and drug to the surface of a rotating agar plate one on top of another in such a way that a uniform density of bacteria is exposed to a logarithmically decreasing volume of drug. Following an incubation of 48 hr at 37 degrees C, the plates are scanned by a laser counter, and the data are subjected to a computerized analysis. Petri plates of 15 cm diameter were used to provide a concentration range of about 250-fold per plate. The Salmonella were concentrated 20-fold to increase sensitivity. Thirty-eight compounds from a variety of chemical classes, including both pharmaceuticals and known mutagens of moderate to strong potency, were tested in both the spiral and the standard pour-plate assays. There was overall test agreement on positive or negative results for 82% of the compounds tested. When only the results from strains TA98 plus TA100 were considered, the agreement was 87%. When positive results were obtained, the fold increase over vehicle control was on average twice as great for the spiral assay compared to the pour-plate assay. It was concluded that the two assay procedures generally provided comparable results, with the spiral assay being somewhat more sensitive in terms of dose-response than the pour-plate assay.

Comparison of the results of a modified miniscreen and the standard bacterial reverse mutation assays.

The bacterial reverse mutation assay (Ames test) provides a rapid assessment of the mutagenic potential of chemicals. The assay is widely used in the pharmaceutical industry for early assessment during candidate compound selection and for regulatory drug submissions. Early in development, many candidate compounds are available in only very small quantities. The use of the standard plate incorporation bacterial reverse mutation assay for screening, using only a single petri plate per concentration, requires the use of approximately 140 mg of test compound to test up to a stock concentration of 100 mg/ml (5000 microg/plate) in five strains of bacteria. A modification of the existing Ames Miniscreen assay has been developed using six-well cell-culture dishes that requires only 21 mg of compound to test a stock concentration of up to 100 mg/ml (2000 microg/well) in three strains of bacteria. The standard plate incorporation assay and the modified Miniscreen assays conducted on proprietary compounds without and with metabolic activation have yielded a high degree of concordance in findings.

Flow cytometric enumeration of micronucleated reticulocytes: high transferability among 14 laboratories.

This laboratory previously described a single-laser flow cytometric method, which effectively resolves micronucleated erythrocyte populations in rodent peripheral blood samples. Even so, the rarity and variable size of micronuclei make it difficult to configure instrument settings consistently and define analysis regions rationally to enumerate the cell populations of interest. Murine erythrocytes from animals infected with the malaria parasite Plasmodium berghei contain a high prevalence of erythrocytes with a uniform DNA content. This biological model for micronucleated erythrocytes offers a means by which the micronucleus analysis regions can be rationally defined, and a means for controlling interexperimental variation. The experiments described herein were performed to extend these studies by testing whether malaria-infected erythrocytes could also be used to enhance the transferability of the method, as well as control intra- and interlaboratory variation. For these studies, blood samples from mice infected with malaria, or treated with vehicle or the clastogen methyl methanesulfonate, were fixed and shipped to collaborating laboratories for analysis. After configuring instrumentation parameters and guiding the position of analysis regions with the malaria-infected blood samples, micronucleated reticulocyte frequencies were measured (20,000 reticulocytes per sample). To evaluate both intra- and interlaboratory variation, five replicates were analyzed per day, and these analyses were repeated on up to five separate days. The data of 14 laboratories presented herein indicate that transferability of this flow cytometric technique is high when instrumentation is guided by the biological standard Plasmodium berghei.

Adult attachment styles: their relations to family context and personality.

This study used a sample of 304 adults to examine mean differences in family climate and personality variables on the basis of individuals' attachment styles. Also examined was whether mean differences varied by age group. Findings showed significant main effects of attachment style, but no Attachment Style x Age Group interactions. Compared with adults with an insecure attachment style, persons with a secure attachment style described their family of origin and their current family more positively and scored higher on personality variables indicative of self-confidence, psychological well-being, and functioning in the social world. When the family climate and personality variables were included in a discriminant function analysis, 2 significant functions were obtained. The 1st function discriminated adults with a positive self-model from those with a negative self-model. The 2nd function contrasted participants with a positive other-model from those with a negative other-model. Thus, this study provided evidence in support of the self- and other-models as the fundamental dimensions of adults' attachment system.

Age and sex differences in strategies of coping and defense across the life span.

Age and sex differences in the use of coping and defense strategies were examined in life-span sample of 381 individuals. Participants responded to 2 self-report measures assessing mechanisms of coping and defense and measures assessing their level of cognitive complexity. Older adults used a combination of coping and defense strategies indicative of greater impulse control and the tendency to positively appraise conflict situations. Adolescents and younger adults used strategies that were outwardly aggressive and psychologically undifferentiated, indicating lower levels of impulse control and self-awareness. Women used more internalizing defenses than men and used coping strategies that flexibly integrated intra-and interpersonal aspects of conflict situations. Taken together, findings provide evidence for the age- and sex-specific use of strategies of coping and defense, suggesting that men and women may face different developmental tasks in the process toward maturity in adulthood.

Self-concept differentiation across the adult life span.

This study used 2 measures to examine 158 adults' (80 men, 78 women; ages 20 to 88 years) self-concept differentiation (SCD) across 5 role-specific self-representations. Findings revealed that the 2 measures did not assess SCD in similar ways and that they showed different associations with age. Specifically, the 1st measure was not significantly related to age, whereas the 2nd measure showed a curvilinear, U-shaped association with age. The 2nd SCD index also showed significant associations with several measures of emotional adjustment and 6 dimensions of psychological well-being. Additional analyses showed that age moderated the associations between SCD and positive and negative psychological well-being. A high level of SCD was associated with lower positive and higher negative psychological well-being for both young and older adults. However, this effect was significantly more pronounced in older adults.

Everyday problem solving in older adults: observational assessment and cognitive correlates.

Older adults' ability to solve practical problems in 3 domains of daily living was assessed using a new measure of everyday problem solving, the Observed Tasks of Daily Living (OTDL). Findings showed that the OTDL formed internally consistent scales representing 3 distinct factors of everyday problem solving. Moreover, the OTDL showed convergent validity with related scales of a paper-and-pencil test. Older adults' performance on the OTDL was significantly correlated with their scores on measures of basic mental abilities. Path analysis showed that age affected older adults' performance on the OTDL directly and indirectly via cognitive abilities. Participants' education and health affected their everyday competence indirectly through cognitive abilities. The effects of perceptual speed and memory span were mediated by fluid and crystallized intelligence.

Representations of self across the life span.

This research extends a cognitive-developmental approach to examining age differences in self-representation from adolescence to mature adulthood and later life. The authors suggest that mature adults move from representations of self that are relatively poorly differentiated from others or social conventions to ones that involve emphasis on process, context, and individuality. Participants (n men = 73, n women = 76), ranging in age from 11 to 85 years, provided spontaneous accounts of their self-representations and responded to measures assessing cognitive and emotional functioning and broad dimensions of personality. On average, self-representation scores peaked in middle-aged adults and were lowest in the preadolescent and older adult age groups. Level of self-representation was related to cognitive and personality variables, but there was some evidence that the pattern of correlates shifted from younger (ages 15-45) to older (ages 46-85) age segments.

Everyday competence in later life: current status and future directions.

This article reviews the literature on the antecedents and outcomes of everyday competence in later life and discusses future directions. It is argued that there is a fairly solid knowledge base with regard to the antecedents and outcomes but not in terms of the components and mechanisms of older adults' everyday competence. Five key issues are identified and discussed in terms of a future research agenda. For each key issue, directions for future research are outlined and a transactional approach is advocated. It is emphasized that older adults should be viewed as proactive individuals who are motivated to minimize the losses and maximize the gains associated with the aging process.

The influence of thyroglobulin on functional imaging in differentiated thyroid cancer.

AIM: Recombinant human thyroid stimulating hormone (rhTSH) for an exogenous stimulation of TSH and consequent thyroglobulin (hTG) synthesis has reinitiated a discussion about the usefulness of diagnostic procedures for the follow-up of differentiated thyroid cancer (DTC). METHOD: Fifty consecutive patients with DTC who received whole-body iodine scintigraphy (WBS) and positron emission tomography (PET) were evaluated. RESULTS: The work-up was normal in 18/50. In 32 patients, functional imaging detected DTC. In 44% exogenous TSH stimulation with rhTSH was used and thyroxin was withdrawn in the others. The hTG under stimulation ranged from 0.8 to 5.004 ng x ml(-1). It was below 2 ng x ml(-1) in four (12.5%) patients. In total, 91 tumour sites were identified by positron emission tomography (PET) and 47 sites by WBS. PET and WBS showed corresponding uptake in 38% of lymph node, 48% of parenchymal and 43% of bone metastases. PET detected additional 53% of lymph node (WBS 9%), 38% of parenchymal (WBS 14%) and 28.5% of bone metastases. CONCLUSION: It is concluded that PET is more sensitive than WBS for the detection of DTC. The follow-up of DTC patients with hTG levels alone misses a significant number of true positive cases. Its use should therefore be restricted to selected low risk patients only.

Age differences in adult personality: findings from the United States and China.

This study used samples of adults from the United States (n = 285) and the People's Republic of China (n = 450) to examine age, gender, and culture differences in personality. Participants in both samples ranged from 20 to 87 years of age and responded to the California Psychological Inventory (CPI). Factor analyses of the CPI resulted in 4 personality factors (i.e., extraversion, control/norm orientation, flexibility, femininity/masculinity), with high congruence across cultures after targeted rotation. Multivariate analyses of variance with scale scores revealed significant Age Group 3 Culture and Gender 3 Culture interactions, and significant main effects of age, gender and culture. Specifically, negative age differences were found for scales that loaded on extraversion and flexibility, with older adults having lower scores on these scales. In contrast, positive age differences were found for scales indicative of control/norm orientation. In general, age differences were more pronounced for Chinese adults than for U.S. adults.