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Swimmer athletes showed a decreased ventilatory response and reduced sympathetic activation during peripheral hypoxic chemoreflex stimulation. Based on these observations, we hypothesized that swimmers develop a diminished cardiorespiratory coupling due to their decreased hypoxic peripheral response. To resolve this hypothesis, we conducted a study using coherence time‐varying analysis to assess the cardiorespiratory coupling in swimmer athletes. We recruited 12 trained swimmers and 12 control subjects for our research. We employed wavelet time‐varying spectral coherence analysis to examine the relationship between the respiratory frequency (Rf) and the heart rate (HR) time series during normoxia and acute chemoreflex activation induced by five consecutive inhalations of 100% N2. Comparing swimmers to control subjects, we observed a significant reduction in the hypoxic ventilatory responses to N2 in swimmers (0.012 ± 0.001 vs. 0.015 ± 0.001 ΔVE/ΔVO2, and 0.365 ± 0.266 vs. 1.430 ± 0.961 ΔVE/ΔVCO2/ΔSpO2, both p < 0.001, swimmers vs. control, respectively). Furthermore, the coherence at the LF cutoff during hypoxia was significantly lower in swimmers compared to control subjects (20.118 ± 3.502 vs. 24.935 ± 3.832 area under curve [AUC], p < 0.012, respectively). Our findings strongly indicate that due to their diminished chemoreflex control, swimmers exhibited a substantial decrease in cardiorespiratory coupling during hypoxic stimulation. [ABSTRACT FROM AUTHOR]

The off‐label use of imiquimod (IQ) for hemangioma treatment has shown clinical benefits. We have previously reported a selective direct IQ‐cytotoxic effect on transformed (H5V) vs. normal (1G11) endothelial cells (EC). In the present study, we investigated the mechanism underlying this selective cytotoxicity in terms of TLR7/8 receptor expression, NF‐κB signalling and time‐dependent modifications of oxidative stress parameters (ROS: reactive oxygen species, catalase and superoxide dismutase activities, GSH/GSSG and lipid peroxidation). TLR7/8 level was extremely low in both cell lines, and IQ did not upregulate TLR7/8 expression or activate NF‐κB signalling. IQ significantly induced ROS in H5V after 2 h and strongly affected antioxidant defenses. After 12 h, enzyme activities were restored to baseline levels but a robust drop in GSH/GSSG persisted together with increased lipid peroxidation levels and a marked mitochondrial dysfunction. Although in normal IQ‐treated EC some oxidative stress parameters were affected after 4 h, mitochondrial health and GSH/GSSG ratio remained notably unaffected after 12 h. Therefore, the early alterations (0–2 h) in transformed EC breached redox homeostasis as strongly as to enhance their susceptibility to IQ. This interesting facet of IQ as redox disruptor could broaden its therapeutic potential for other skin malignancies, alone or in adjuvant schemes. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the acute effects of high‐intensity interval training (HIIT) exercise and endurance exercise (EE) on pulmonary function, sympathetic/parasympathetic balance, and cardiorespiratory coupling (CRC) in healthy participants. Using a crossover repeated‐measurements design, four females and four males were exposed to EE (20 min at 80% maximal heart rate [HR]), HIIT (1 min of exercise at 90% maximal HR per 1 min of rest, 10 times), or control condition (resting). Pulmonary function, HR, CRC, and heart rate variability (HRV) were assessed before and after the interventions. Results revealed no significant effects of EE or HIIT on pulmonary function. The EE, but not HIIT, significantly increased CRC. In contrast, HRV was markedly changed by HIIT, not by EE. Indeed, both the low‐frequency (LFHRV) and high‐frequency (HFHRV) components of HRV were increased and decreased, respectively, after HIIT. The increase in LFHRV was greater after HIIT than after EE. Therefore, a single bout of HIIT or EE has no effects on pulmonary function. Moreover, CRC and cardiac autonomic regulation are targeted differently by the two exercise modalities. [ABSTRACT FROM AUTHOR]

IV iron is indicated in clinical conditions, where rapid anaemia alleviation and repletion of iron stores are required. The acute toxicity of IV iron is ascribed to the presence of labile iron in plasma. Thus, shorter plasma residence time might improve the safety profile, even for compounds holding‐on the iron tightly. In this single‐centre, open‐label, single‐dose escalation study, we evaluated the elimination kinetics of ferric bepectate (FBP) compared to those of ferric carboxymaltose (FCM). Thirty‐three iron‐depleted anaemic patients who had undergone cardiac surgery were included and received 200, 500 or 1500 mg FBP or 500 mg FCM. Plasma drug curves were subjected to model‐free analysis. Because saturation kinetics was found, a compartmental model with limited elimination capacity was applied. Urinary iron excretion was also analysed. The initial non‐compartmental analysis revealed an increasing AUC/dose ratio for FBP. For both drugs, the central distribution compartment corresponded to plasma volume, and elimination followed Michaelis‐Menten saturation kinetics. Maximal elimination rates (Vmax) were 224 mg/h and 81 mg/h for FBP 500 mg and FCM 500 mg, respectively; drug concentrations at half Vmax (Km), 99 mg/L and 212 mg/L, respectively; and terminal plasma half‐life (T½), 3.05 h and 8.96 h, respectively. Both drugs were equally effective in eliciting an early ferritin rise. Urinary iron excretion was measurable in all patients receiving FCM but not in those receiving FBP, which was well tolerated. Intravenous iron drugs are subject to capacity‐limited elimination with different saturation thresholds. Urinary iron excretion can be used as a surrogate for labile plasma iron. [ABSTRACT FROM AUTHOR]

In major orthopaedic surgery, it is recommended to detect and correct preoperative anaemia several weeks prior to surgery. However, in many cases, the procedure is urgent or the patient is evaluated shortly before the intervention. As iron deficiency is the leading cause of perioperative anaemia, an exhaustive review of the literature was performed to assess the efficacy and safety of short‐term perioperative intravenous, with or without erythropoietin, or postoperative oral or intravenous supplementation in major orthopaedic surgery. Overall, 20 studies met the inclusion criteria. There were 13 randomized trials (moderate quality) and seven observational studies (low to very low quality). The primary outcomes were reduction in transfusion requirements, haemoglobin increase and medication side‐effects during the study period. Data analysis showed that postoperative oral iron administration neither increased haemoglobin nor reduced transfusion requirements, and it was associated with significant gastrointestinal adverse effects (15%). In contrast, for some patient populations, perioperative or postoperative administration of intravenous iron, with or without recombinant erythropoietin, may reduce transfusion requirements and/or hasten the recovery from postoperative, with few clinically relevant adverse effects (<2%). However, discrepancies between randomized trials and observational studies on the possible beneficial effects of short‐term perioperative intravenous iron administration were found for patients undergoing surgery for hip fracture repair. Further studies are needed to elucidate when the treatment should be started, which combination of drugs should be used, and which patient groups would be most benefit. [ABSTRACT FROM AUTHOR]

An Implicit Association Test was developed to assess the mental illness stigma in people from the general population, mental health professionals, people with a diagnosis, and family members. No differences were found between groups. Implicit stigma was found throughout the sample, with lower scores in the younger age group. [ABSTRACT FROM AUTHOR]

Background: Preoperative anemia prevalence among colorectal cancer (CRC) patients is high and may adversely influence postoperative outcome. This study assesses the efficacy of a preoperative anemia managing protocol in CRC.Study Design and Methods: This was a retrospective analysis of consecutive CRC resections at two Spanish centers (January 2012 to December 2013). Preoperative anemia was defined as a hemoglobin (Hb) level of less than 13 g/dL and treated with intravenous iron (IVI) or standard care (oral iron or no iron). Red blood cell transfusion (RBCT) requirements was the primary outcome variable. Postoperative infection rate and length of hospital stay (LOS) were secondary outcome variables. Patients were managed with a restrictive transfusion trigger (Hb < 8 g/dL). Infection was diagnosed clinically and confirmed by laboratory, microbiologic, and/or radiologic evidence.Results: Overall, 322 of 571 patients (56%) presented with anemia: 232 received IVI and 90 standard care. There were differences in RBCT rate between no anemia and anemia (2% vs. 16%; p < 0.01), but not in postoperative infections (19% vs. 22%; p = NS) or LOS. Compared to those on standard care, anemic patients on IVI presented with lower Hb (10.8 g/dL vs. 12.0 g/dL; p < 0.001) at baseline, but similar Hb on day of surgery and Postoperative Day 30. There were no between-group differences in RBCT rates (16% vs. 17%; p = NS), but infection rates were lower among IVI-treated patients (18% vs. 29%; p < 0.05). No relevant IVI-related side effects were recorded.Conclusion: Compared to standard care, IVI was more effective in treating preoperative anemia in CRC patients and appeared to reduce infection rate, although it did not reduce postoperative RBCT. [ABSTRACT FROM AUTHOR]

Test the proposed dose regimens with respect to proportionality between dose and early after dosing plasma drug concentration in a dose range from 10 times below up to maximal dose allowed. Thus, a linear relation between the intravenous drug dose and the maximal after dosing drug concentration would be expected. Both labile and free iron in plasma may be toxic.1 Thus, intravenous iron drugs should be formulated to avoid its release iron into plasma. [Extracted from the article]

An introduction to the journal is presented in which the editor discusses the efficacy of ferric carboxymaltose with or without recombinant human erythropoietin in the reduction of allogeneic blood transfusion after repair of hip fracture.

Macrophage migration to the focus of infection is a hallmark of the innate immune response. Macrophage spreading, adhesion, and migration through the extracellular matrix require dynamic remodeling of the actin cytoskeleton associated to integrin clustering in podosomes and focal adhesions. Here, we show that prostaglandin E2 (PGE2), the main prostaglandin produced by macrophages during inflammation, promote the distinctive dose-dependent formation of podosomes or focal adhesions in macrophages. Low concentrations of PGE2 increased p110γ PI3K expression, phosphorylation of actin-related protein 2, and formation of podosomes, which enhanced macrophage migration in response to chemokines. However, high doses of PGE2 increased phosphorylation of paxillin and focal adhesion kinase, the expression of serine/threonine protein kinase 1, and promoted focal adhesion formation and macrophage adhesion, reducing macrophage chemotaxis. In summary, we describe the dual role of PGE2 as a promoter of macrophage chemotaxis and adhesion, proposing a new model of macrophage migration to the inflammatory focus in the presence of a gradient of PGE2. [ABSTRACT FROM AUTHOR]

Coupling of transcription and alternative splicing via regulation of the transcriptional elongation rate is a well-studied phenomenon. Template features that act as roadblocks for the progression of RNA polymerase II comprise histone modifications and variants, DNA-interacting proteins and chromatin compaction. These may affect alternative splicing decisions by inducing pauses or decreasing elongation rate that change the time-window for splicing regulatory sequences to be recognized. Herein we discuss the evidence supporting the influence of template structural modifications on transcription and splicing, and provide insights about possible roles of non-B DNA conformations on the regulation of alternative splicing. [ABSTRACT FROM AUTHOR]

Background Postoperative nosocomial infection ( PNI) is a severe complication in surgical patients. Known risk factors of PNI such as allogeneic blood transfusions ( ABTs), anemia, and iron deficiency are manageable with perioperative intravenous ( IV) iron therapy. To address potential concerns about IV iron and the risk of PNI, we studied a large series of orthopedic surgical patients for possible relations between IV iron, ABT, and PNI. Study Design and Methods Pooled data on ABT, PNI, 30-day mortality, and length of hospital stay ( LHS) from 2547 patients undergoing elective lower-limb arthroplasty (n = 1186) or hip fracture repair (n = 1361) were compared between patients who received either very-short-term perioperative IV iron (200-600 mg; n = 1538), with or without recombinant human erythropoietin (rHuEPO; 40,000 IU), or standard treatment (n = 1009). Results Compared to standard therapy, perioperative IV iron reduced rates of ABT (32.4% vs. 48.8%; p = 0.001), PNI (10.7% vs. 26.9%; p = 0.001), and 30-day mortality (4.8% vs. 9.4%; p = 0.003) and the LHS (11.9 days vs. 13.4 days; p = 0.001) in hip fracture patients. These benefits were observed in both transfused and nontransfused patients. Also in elective arthroplasty, IV iron reduced ABT rates (8.9% vs. 30.1%; p = 0.001) and LHS (8.4 days vs.10.7 days; p = 0.001), without differences in PNI rates (2.8% vs. 3.7%; p = 0.417), and there was no 30-day mortality. Conclusion Despite known limitations of pooled observational analyses, these results suggest that very-short-term perioperative administration of IV iron, with or without rHuEPO, in major lower limb orthopedic procedures is associated with reduced ABT rates and LHS, without increasing postoperative morbidity or mortality. [ABSTRACT FROM AUTHOR]

Summary In Caenorhabditis elegans, the insulin/IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin/IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of the insulin/IGF pathway or by a reduction in the activity of the nuclear hormone receptor daf-12. We have isolated a pkc-1 mutant that acts as a novel suppressor of the dauer phenotypes caused by insulin/IGF receptor mutations. Interactions between insulin/IGF mutants and the pkc-1 suppressor mutant are similar to those described for daf-12 or the DAF-12 coregulator din-1. Moreover, we show that the expression of the DAF-12 target daf-9, which is normally elevated upon a reduction in insulin/IGF receptor activity, is suppressed in a pkc-1 mutant background, suggesting that pkc-1 could link the daf-12 and insulin/IGF pathways. pkc-1 has been implicated in the regulation of peptide neurosecretion in C. elegans. Although we demonstrate that pkc-1 expression in the nervous system regulates dauer formation, our results suggest that the requirement for pkc-1 in neurosecretion is independent of its role in modulating insulin/IGF signalling. pkc-1 belongs to the novel protein kinase C (nPKC) family, members of which have been implicated in insulin resistance and diabetes in mammals, suggesting a conserved role for pkc-1 in the regulation of the insulin/IGF pathway. [ABSTRACT FROM AUTHOR]

Preoperative anemia in patients undergoing cardiac surgery is associated with a higher transfusion risk and poorer outcomes. This retrospective study was undertaken to assess the prevalence of preoperative anemia and its associated risk factors, as well as its influence on postoperative outcomes, in 576 patients undergoing elective cardiac surgery (52.3% with cardiopulmonary bypass) for myocardial revascularization, valve replacement, coronary + valve, or miscellaneous pathology at a single institution. Perioperative data were reviewed according to the presence or absence of preoperative anemia (hemoglobin < 13 g/dL for men, hemoglobin < 12 g/dL for women). Overall, 210 patients (36.5%) presented with anemia. Logistic regression analysis revealed that age, chronic kidney disease, and consumption of proton pump inhibitors histamine H2 receptor antagonists and diuretics were independent risk factors for the presence of preoperative anemia. Postoperatively, anemic patients received transfusions and inotropic support and stayed longer than 4 days in the recovery unit more frequently than non-anemic patients, but there were no differences in the composite outcome variable (stroke, myocardial infarction, renal failure or death). In conclusion, our data seem to indicate that preoperative anemia has a high prevalence among elective cardiac surgical patients and increases postoperative morbidity. Therefore, we need to address two specific areas about preoperative anemia in these patients: early recognition and evaluation, and appropriate and timely treatment. [ABSTRACT FROM AUTHOR]

Preoperative anemia is an independent risk factor for allogeneic blood transfusion in patients undergoing major orthopedic surgery (MOS) whereas hematinic deficiency can delay the recovery from postoperative anemia. Both conditions can, however, be corrected before elective procedures are undertaken. We therefore evaluated the prevalence of anemia and hematinic deficiencies in MOS patients. Demographic and laboratory data were gathered from all MOS patients from a single institution between January 2001 and December 2002. A total of 715 patients (483 women/232 men) entered the study. According to WHO criteria, the prevalence of anemia was 10.5% and increased with age, without gender-related differences. Preoperative hemoglobin was < 13 g/dL in 19.4% of patients, and the prevalence of hematinic deficiencies was 33% for iron, 12.3% for vitamin B12 and 3% for folate. In anemic patients, there were 30.8% with hematinic deficiency anemia (20% with iron-deficiency anemia), 30.8% with anemia of chronic disease and 38.4% with anemia of mixed or indeterminate cause. The prevalence of anemia, as well as of hematinic deficiencies, is high in MOS patients. Therefore, whenever possible, patients undergoing MOS should be assessed early enough to allow for proper investigation and treatment prior to the scheduled procedure. [ABSTRACT FROM AUTHOR]

Shoulder arthroplasty may be associated with considerable blood loss, and some patients require allogeneic blood transfusion (ABT). However, there is almost no information available for proximal humerus fracture (PHF) repair surgery. We therefore evaluated the influence of two transfusion protocols on ABT requirements in patients undergoing hemiarthroplasty surgery for PFH. We assessed the requirements for ABT in 78 patients receiving hemiarthroplasty for PHF, who were managed with a conservative transfusion protocol [hemoglobin(Hb) < 9.0 g/dL; group 1; n = 31] or a restrictive transfusion protocol (Hb < 8.0 g/dL and/or clinical signs/symptoms of anemia/hypoxemia; group 2; n = 47). Overall, the ABT rate (12% vs. 48%; P = 0.001) and the transfusion index (0.2 ± 0.7 vs. 0.9 ± 1.0 unit/patient; P = 0.001) were lower in group 2 than in group 1. The differences in transfusion rate and transfusion index between groups were significant for patients with Hb < 13.0 g/dL (75% vs. 18%, for groups 1 and 2, respectively; P = 0.001), but not for those with Hb ≥ 13.0 g/dL (20% vs. 7%; P = 0.180). The implementation of a restrictive transfusion protocol seems to be effective in reducing ABT, especially in PHF patients with preoperative Hb < 13.0 g/dL. [ABSTRACT FROM AUTHOR]

We prospectively investigated the utility of preoperative intravenous (IV) iron treatment to increase hemoglobin (Hb) levels and reduce the need for transfusion in women with iron deficiency anemia (IDA) or iron deficiency (ID) scheduled for elective abdominal hysterectomy. Seventy-five women with ID or IDA were enrolled in the study. Women having their surgical procedure at least 1 month after preoperative assessment received IV iron sucrose during 2–4 weeks (IV iron group, n = 31). Women having their surgical procedure a few days after preoperative assessment did not receive IV iron (control group, n = 44). At baseline, there were no differences between the two groups in terms of weight or age, prevalence of anemia, Hb levels or iron laboratory parameters. IV iron sucrose (760 ± 290 mg) increased preoperative Hb (ΔHb: 2.2 ± 1.2 g/dL; P < 0.001) and reduced postoperative transfusion rates when compared with the control group (32% vs. 0%, respectively; P < 0.001). In addition, fewer women from the IV iron group were anemic on postoperative day 21 (23% vs. 68%, respectively; P < 0.01). No life-threatening iron sucrose adverse effect was observed. Because of the rapid increase in Hb levels, IV iron sucrose administration seems to be an effective approach for treating preoperative anemia and reducing transfusion rates in this female population. [ABSTRACT FROM AUTHOR]

The Consensus Document on Alternatives to Allogeneic Blood Transfusion (AABT) has been drawn up by a panel of experts from five scientific societies. The Spanish societies of anesthesiology (SEDAR), critical care medicine and coronary units (SEMICYUC), hematology and hemotherapy (AEHH), blood transfusion (SETS), and thrombosis and hemostasis (SETH) have sponsored and participated in this consensus document. Alternatives to blood transfusion have been divided into pharmacological and nonpharmacological, with four modules and 12 topics. The main objective variable was the reduction of allogeneic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi methodology, which classifies the grades of recommendation from ‘A’ (supported by controlled studies) to ‘E’ (noncontrolled studies and expert opinion). The experts concluded that most of the indications for AABT only attained middle or low grades of recommendation, ‘C’, ‘D’ or ‘E’, thus indicating the need for further controlled studies. [ABSTRACT FROM AUTHOR]

In patients undergoing total knee replacement (TKR), most of blood loss occurs during the postoperative period and 30–50% of these patients receive allogeneic blood transfusion (ABT). For this reason, salvage and return of washed shed blood (WSB) from postoperative drainage may represent an alternative to ABT in these patients. We have, therefore, evaluated the clinical utility of WSB return in TKR patients. Data from 220 consecutive TKR patients were prospectively collected. WSB salvage and reinfusion ( OrthoPAT, Haemonetics Corp., Braintree, MA, USA) were intended for 115 patients (reinfusion group), whereas the remaining 105 patients served as a control group. Patients received ABT if their hemoglobin concentration was lower than 8.0 g/dL or they showed clinical signs and symptoms of acute anemia. WSB return was possible in 97 patients who received a mean of 283 ± 180 mL of red cells (hematocrit, 66% ± 4%), without any clinically relevant incident. Return of WSB decreased both the ABT rate (50% vs. 19%, for control and reinfusion groups, respectively; P < 0.01) and the ABT index (0.86 ± 0.99 vs. 0.35 ± 0.83 units/patient, respectively; P < 0.01). In addition, when compared with those in the control group, patients in the reinfusion group had less postoperative infections (11.4% vs. 4.3%; P < 0.05), recovered the ability to walk 1 day earlier ( P < 0.01), and had shorter hospital stay ( P < 0.01). Return of WSB after TKR seems to effectively reduce postoperative requirements for ABT. However, for patients with preoperative hemoglobin concentrations below 13.0 g/dL, additional blood-saving methods should be combined with WSB return. [ABSTRACT FROM AUTHOR]

Salvage and return of unwashed filtered shed blood (USB) after unilateral total knee replacement (TKR) is a blood-saving method frequently used to avoid allogeneic blood transfusion (ABT). However, the use of USB is controversial, as it may impair hemostasis when retransfused. We report on 1-month follow-up of fibrinolytic activity in TKR patients who received either ABT, USB or no transfusion. One hundred and six consecutive TKR patients entered the study: 88 received no transfusion (group 1), five received ABT (group 2), and 13 received USB (group 3). Blood samples were obtained on day of surgery and postoperative days 1, 7 and 30, and assayed for blood counts, C-reactive protein (CRP), and D-dimers. Demographic and clinical data were also collected. There were no differences in demographic data or postoperative infection rate between groups, but length of hospital stay was longer in group 2 ( P < 0.05). Postoperative levels of D-dimers increased on day 1, and remained elevated on day 30 in all groups, but on day 1 they were higher in group 3 ( P < 0.05). There were no differences in perioperative levels of CRP between groups, and they correlated with D-dimers both preoperatively and on day 30. Taken together, these data suggest that surgery for TKR induced an activation of coagulation and fibrinolysis. This situation lasts at least as late as 30 days after surgery, and is not modified by transfusion, except for a transitory induction of fibrinolysis by USB return in the early postoperative period. [ABSTRACT FROM AUTHOR]

BACKGROUND: Unilateral total knee replacement (TKR) results in a substantial blood loss and 30 to 50 percent of patients receive allogeneic blood transfusion (ABT). Therefore, the effectiveness of a restrictive transfusion trigger (hemoglobin [Hb] level < 8 g/dL) plus stimulation of erythropoiesis was evaluated, with or without blood salvage, for reducing ABT in TKR patients. STUDY DESIGN AND METHODS: A series of 139 consecutive of primary TKR patients received perioperative iron sucrose (2 × 200 mg/48 hr, intravenously [IV]), plus preoperative erythropoietin (EPO; 1 × 40.000 UI, sc) if preoperative Hb level was less than 130 g per L (Group A). This protocol was applied to another series of 173 consecutive TKR patients who also received postoperative unwashed shed blood (USB) if preoperative Hb level was less than 130 g per L (Group B). Perioperative clinical and laboratory data were gathered. RESULTS: No adverse effects of iron sucrose, EPO, or USB administration were witnessed, and only 13 patients received ABT overall (4%). No major differences in perioperative blood counts or iron metabolism variables were observed between groups, but stimulation of erythropoiesis seemed to be more pronounced in those patients receiving EPO (p < 0.05). There were no differences in postoperative complications between groups, but length of hospital stay for patients with a preoperative Hb level of less than 130 g per L was shorter in Group B (p < 0.05). CONCLUSION: This blood saving protocol seems to be effective for reducing ABT in TKR patients. Which patients are more likely to benefit from either perioperative iron administration or selective addition of postoperative blood salvage to pharmacologic treatment, however, needs to be further evaluated. [ABSTRACT FROM AUTHOR]

SUMMARY Perioperative anemia is a common condition among orthopedic and trauma surgery patients. Preoperative anemia is most frequently caused by iron deficiency or chronic inflammatory disease and is one of the major predictive factors for perioperative blood transfusion. In addition to preoperative anemia, perioperative blood loss is a major cause of postoperative anemia although blunted erythropoiesis attributable to inflammation-induced inhibition of erythropoietin (EPO) action and decreased iron availability may also play a role. We assessed the safety and effectiveness of perioperative intravenous iron administration, with or without EPO, to stimulate erythropoiesis in patients undergoing trauma (hip fracture) or elective orthopedic surgery (knee and hip replacement). Overall, no side effects were observed. The treatment resulted in lower transfusion requirements, decreased postoperative infection and mortality rates, and shorter length of hospital stay. If confirmed by large randomized clinical trials, these findings will provide a rationale to treat orthopedic and trauma patients with intravenous iron, alone or in combination with EPO, in order to attain higher postoperative hemoglobin concentrations, reduce postoperative complications and shorten hospital stay while limiting exposure to allogeneic blood. [ABSTRACT FROM AUTHOR]

SUMMARY The increasing number of surgical procedures has raised the demand for allogeneic blood to a level that often exceeds supply. Moreover, 10% of all transfusions are given in the orthopedic surgery setting, requiring the avoidance of liberal transfusion criteria to further reduce the risk of infection and other complications. As a result, a series of blood-conservation measures have been developed. In this article, we review the use of autologous transfusion in orthopedic surgery, with a special focus on perioperative red cell salvage. From data reviewed, it can be concluded that perioperative salvage of blood, either intraoperative cell salvage or postoperative cell salvage, seems to be an excellent source of functional and viable red cells, without many of the transfusion-related risks and with few side effects. The effectiveness of perioperative cell salvage to reduce exposure to allogeneic blood is greatly enhanced by the implementation of a restrictive transfusion protocol and the association with other blood-sparing strategies [preoperative autologous blood donation (PABD), erythropoietin, intravenous iron], especially in anemic patients. Moreover, perioperative cell salvage may reduce the number of required PABD units or render PABD unnecessary. Finally, although formal cost-effectiveness studies on perioperative cell salvage are lacking, based on current allogeneic blood transfusion costs, it is generally accepted that the equivalent of at least one unit of blood needs to be recovered for these techniques to be cost-effective. Therefore, these procedures should be used on a case-by-case basis. [ABSTRACT FROM AUTHOR]

In animal cells, cytokinesis occurs by constriction of an actomyosin ring. In fission yeast cells, ring constriction is triggered by the septum initiation network (SIN), an SPB-associated GTPase-regulated kinase cascade that coordinates exit from mitosis with cytokinesis. We have identified a novel protein, Etd1p, required to trigger actomyosin ring constriction in fission yeasts. This protein is localised at the cell tips during interphase. In mitosis, it relocates to the medial cortex region and, coincident with cytokinesis, it assembles into the actomyosin ring by association to Cdc15p. Relocation of Etd1p from the plasma membrane to the medial ring is triggered by SIN signalling and, reciprocally, relocation of the Sid2p–Mob1p kinase complex from the SPB to the division site, a late step in the execution of the SIN, requires Etd1p. These results suggest that Etd1p coordinates the mitotic activation of SIN with the initiation of actomyosin ring constriction. Etd1p peaks during cytokinesis and is degraded by the ubiquitin-dependent 26S-proteasome pathway at the end of septation, providing a mechanism to couple inactivation of SIN to completion of cytokinesis. [ABSTRACT FROM AUTHOR]

The insulin/insulin-like growth factor-1 (Ins/IGF-1) pathway regulates the aging rate of the nematodeCaenorhabditis elegans. We describe other features of the three Ins/IGF-1 mutantsdaf-2,age-1andaap-1. We show that the investigated Ins/IGF-1 mutants all have a reduced body volume, reduced reproductive capacity, increased ATP concentrations and an elevated stress resistance. We also observed that heat production is lower in these mutants, although the respiration rate was similar or higher compared with wild-type individuals, suggesting a metabolic shift in these mutants. [ABSTRACT FROM AUTHOR]

Symptoms of stress are prevalent among the homeless. Growing evidence suggests that disclosure of traumatic experiences is beneficial to health. This pilot study examined the effects of an emotional disclosure protocol on a group of 8 homeless people, using a single-group design. Clinical effectiveness was evaluated using the Imp act of Event Scale, the Beck Depression Inventory, the Beck Anxiety Inventory, the Perceived Stress Scale, the Reading Span Task, and the Digit Span Test. Participant satisfaction was also measured. Results showed significant improvements in functioning at 1- and 6-week follow-up, and good satisfaction levels. The discussion remarks on the limitations (lack of a control group, small sample size, and other biases) and the need for more research in this topic. [ABSTRACT FROM AUTHOR]

Patients undergoing pertrochanteric hip fracture (PHF) repair surgery often receive perioperative allogeneic blood transfusions (ABTs) to avoid the deleterious effects of anemia. Nevertheless, concerns about adverse effects of ABTs have prompted the review of transfusion practice and the search for a safer treatment of perioperative anemia.The effect of preoperative 200 to 300 mg of intravenous (IV; Group 2; n = 55) iron sucrose administration on transfusion requirements and postoperative morbidity-mortality in patients with PHF has been prospectively investigated. A previous series of 102 PHF patients served as the control group (Group 1). All patients were older than 65 years and were operated on at the third day after admission to the hospital, by the same medical team and with the same implant.Iron sucrose was well tolerated and reduced the transfusion rate in patients with admission hemoglobin levels of greater than 120 g per L (p < 0.05) who also received fewer units of red blood cells (p < 0.05). In addition, iron sucrose reduced postoperative infection rate (p < 0.05), but not 30-day mortality rate or mean length of hospital stay.The administration of IV iron sucrose seems to reduce ABT requirements in patients with PHF and is associated to lower postoperative morbidity. The possible mechanisms involved in these effects are discussed. [ABSTRACT FROM AUTHOR]

Studies the detection and removal of fat particles from postoperative salvaged blood in orthopedic surgery. Controversial issues concerning the blood-saving method; Study design and methods; Features of fat particles in shed blood.

We propose a new approach that permits correlation of specific domains defined by their primary sequence with their location in the structure of complex macromolecular aggregates. It is based on the combination of well-established structural analysis methods that incorporate the use of overlapping peptides on cellulose membranes for the isolation and purification of specific antibodies from a polyclonal antiserum. Monospecific antibodies to the connector protein of bacteriophage Æ29 were isolated from polyclonal antisera using a new development of the spotscan method. These antibodies can be purified in quantities that allow antigenicity testing in enzyme-linked immunosorbent assays, Western blotting and immunoprecipitations, demonstrating the specificity of this isolation procedure. This approach has allowed us to generate direct antibody probes for immunoelectron microscopy mapping of different connector protein domains in a low resolution three-dimensional epitope map. [ABSTRACT FROM PUBLISHER]

R3542 --> Diabetes mellitus (DM) is one of the major public health problems. Glucose variability is of such relevance that vascular complications occurrences in DM patients has been attributed to hyperglycemia and dysglycemia event. Therefore, glycemia variability may be considered a health issue; however, whether glycemia variability is represented by a given pattern oscillation, is yet to be determined. Then, we sought to determine whether glycemic variability, assessed with continuous glucose monitoring (CGM), display a stationary pattern of oscillation with characteristics of circadian rhythm in patients with diabetes mellitus (DM) type I (DM‐I) and type II (DM‐II). The CGM data was assessed every 5 minutes x 24 hours x 6 days. Patients (n=196; age, 18‐80 years) were assigned to DM‐I (n=144, Males: 79), DM‐II (n=24, Males 14) and Control (i.e., healthy; n=28, Males: 6) groups. Circadian rhythm of glycemia was assessed during day (08:00‐20:00 h) and night (20:00‐08:00 h) phases. Anthropometry, pharmacologic treatments, glycosylated hemoglobin (HbA1c), and years of evolution were determined. Participants with DM‐I and DM‐II had greater HbA1c and standard deviation of glycemia compared to Controls, independent of sex. CGM revealed a predominant stationary oscillatory pattern of glycemic control in all experimental groups. Moreover, maximum energy oscillation of glycemia revealed oscillations between 2‐6 days. Between 10:00‐14:00 h DM‐I females displayed greater increase of glycemia compared to DM‐I males and Control females (p<0.05). Females DM‐II patients, between 13:00–19:00 h showed an increase (p<0.05) of glycemia vs. Control females. The DM‐I and DM‐II males, between 02:00‐10:00 h and 22:00‐24:00 h, increased glycemia compared to Control males. The magnitude of interindividual variability of hyperglycemia was similar during day and night phases in DM‐I and DM‐II patients, although in DM‐I male patients hyperglycemia was greater at night compared to day phase (p<0.05). This study demonstrates that the DM‐I and ‐II Female group has a stationary pattern that is characterized by having a circadian pattern. Therefore, the oscillatory pattern reveal that exist a sensitive daily time, which could help to develop new therapeutic strategies to improve the outcome of this critical population. [ABSTRACT FROM AUTHOR]

The article informs that patients require allogeneic blood transfusion (ABT) in case of total knee replacement due to substantial blood loss. It further informs that the blood processing device, OrthoPAT by Haemonetics Corp. which returns the post-operative shed blood to the patients to avoid ABT requirements. It mentions that the unwashed shed blood which is returned with the help of the device indicate lower count of white blood cells, platelets and cytokines.

The authors reflect on the use of postoperative drains following hip replacement surgery. They discuss the prevalence use of postoperative drains, which reduce the occurrence of wound hematoma and infection following surgery. They evaluate the efficacy of postoperative drains, compare the advantages of high-vacuum drainage with low-vacuum drainage, and investigate the significance of low-vacuum reinfusion drains following hip replacement surgery.

A letter to the editor is presented on an issue related to the blood salvage after elective knee arthroplasty.

The article discusses iron content in donated blood. It focuses on future consequence regarding the age limit extension for blood donation. It further mentions that iron deficiency can restrain the donated red blood cell (RBC) mass restoration in volunteer blood donor (VBD) that may lead to iatrogenic anemia, a blood disorder.

A letter to the editor is presented in response to the article about the preoperative autologous blood donation in Spain in the February 2007 issue.

Presents a letter to the editor regarding the use of recombinant human erythropoietin to facilitate autologous blood collections in children undergoing spinal surgery, previously published in the journal "Transfusion."

Circulating miRNAs as diagnostic tool for discrimination of respiratory disease: Asthma, asthma-chronic obstructive pulmonary disease (COPD) overlap and COPD We can conclude that the miRNAs combination is better to differentiate asthma from COPD, whereas miR-320a alone is the most appropriate to differentiate asthma and ACO. In our study, miRNAs expression is even better for asthma discrimination than blood eosinophils, which has an AUC for ACO-asthma of 0.56 and an AUC of COPD-asthma of 0.86. Trying to get an insight into the pathophysiological mechanisms that may differ between asthma and COPD/ACO consequence of these differences in miRNAs expression, we performed target-miRNA analysis by miRSystem. [Extracted from the article]

The article lists the names of reviewers to express grattitude including Jason Acker, Judith Aeschlimann, and Anurag Agrawal.