Monoclonal antibodies to fibrillin 1 (MP340), a component of elastin-associated microfibrils, were used to screen cDNA libraries made from bovine nuchal ligament mRNA. One of the selected clones ...(cL9; 1.2 kb) hybridized on Northern (RNA) blotting with nuchal ligament mRNA to two abundant mRNAs of 9.0 and 7.5 kb, which were clearly distinct from fibrillin mRNA (10 kb). Further library screening and later reverse transcription PCR by the rapid amplification of cDNA ends (RACE) technique resulted in the isolation of additional overlapping cDNAs corresponding to about 6.7 kb of the mRNA. The encoded protein exhibited sequence similarity of around 80% with a recently identified human protein named latent transforming growth factor β1 (TGF-β1)-binding protein 2 (LTBP-2), indicating that the new protein was bovine LTBP-2. This was confirmed by the specific localization of bovine LTBP-2 cDNA probes to human chromosome 14q24.3, which is the locus of the human LTBP-2 gene. The domain structure of bovine LTBP-2 is very similar to that of the human LTBP-2, containing 20 examples of 6-cysteine epidermal growth factor-like repeats, 16 of which have the consensus sequence for calcium binding, together with 4 examples of 8-cysteine motifs characteristic of fibrillins and LTBP-1. A 4-cysteine sequence which is unique to bovine LTBP-2 and which has similarity to the 8-cysteine motifs was also present. Antibodies raised to two unique bovine LTBP-2 peptides specifically localized in tissue sections to the elastin-associated microfibrils, indicating that LTBP-2 is closely associated with these structures. Immunoblotting experiments identified putative LTBP-2 isoforms as a 260-kDa species released into the medium by cultured elastic tissue cells and as larger 290- and 310-kDa species in tissue extracts. A major proportion of tissue-derived LTBP-2 required treatment with 6 M guanidine for solubilization, indicating that the protein was strongly bound to the microfibrils. Most of the guanidine-solubilized LTBP-2 appeared to be monomeric, indicating that it was not involved in disulfide-bonded aggregation either with itself or with latent TGF-β. Additional LTBP-2 was resistant to solubilization with 6 M guanidine but was readily extracted with a reductive saline solution. This treatment is relatively specific for solubilization of microfibrillar constituents including fibrillin 1 and microfibril-associated glycoprotein. Therefore, it can be inferred that some LTBP-2 is bound covalently to the microfibrils by reducible disulfide linkages. The evidence suggests that LTBP-2 has a direct role in elastic fiber structure and assembly which may be independent of its growth factor-binding properties. Thus, LTBP-2 appears to share functional characteristics with both LTBP-1 and fibrillins.
Dogs exhibit both neuroanatomical and cognitive changes as a function of age that parallel those seen in aging humans. This study describes in vivo changes in neuroanatomical and cerebrovascular ...characteristics of the canine brain as a function of age in a group of dogs ranging from 4 to 15 years old. Dynamic contrast-enhanced magnetic resonance imaging (MRI) was used to measure the kinetics of contrast agents in the brain. Measures of vascular volume and blood-brain barrier (BBB) permeability were derived from a pharmacokinetic analysis. Cortical atrophy and ventricular enlargement were characteristic features of the aged canine brain. Vascular volume did not vary as a function of age and BBB permeability exhibited a nonsignificant increasing trend with age. However, BBB dysfunction was detected in one middle-aged dog that in addition to having unusually large ventricles, demonstrated an early onset of diffuse senile plaques at postmortem. These findings indicate that BBB dysfunction detected by magnetic resonance imaging may be useful for predicting and potentially diagnosing early pathological conditions.
Assessment of an older person's condition may be difficult, as signs and symptoms may be vague and nonspecific. Acute confusion or delirium in the older patient is a common problem in the emergency ...department and can be the main sign underlying a number of serious conditions. Here, Shanley et al stress that nurses need to pay careful attention to functional and cognitive status as well as polypharmacy and falls. Frail older persons in the emergency department are prone to problems in basic care such as position change and pressure area care, nutrition, toileting, and orientation if confused.
Abstract 3453
Individuals undergoing allogeneic transplantation receive multiple red blood cell transfusions both as part of the transplant procedure and as part of the pre-transplant care of the ...underlying disease. Therefore these patients may be at risk for complications of transfusional iron overload. Several studies have noted that individuals entering the transplant with baseline elevated serum ferritin values have decreased overall survival and higher rates of disease relapse. Whether the iron is a direct contributor to inferior outcomes or is a marker of more advanced disease (thereby requiring greater transfusions) is unclear. Little is known about the incidence and consequences of iron overload among long-term survivors of allogeneic transplantation.
Using Kaplan-Meier and Cox regression analyses, we performed a single center, retrospective cohort study of consecutive allogeneic transplants performed at Hackensack University Medical Center from January 2002 through June 30, 2009 to determine the association between serum ferritin (measured approximately 1 yr post allogeneic transplant) and overall survival.
During the study time frame, 637 allogeneic transplants (Donor Lymphocyte Infusion procedures excluded) were performed at our center and 342 (54%) survived ≥ one year. Among 1-year survivors 240 (70%) had post-transplant serum ferritin values available for review, including 132 (55%) allogeneic sibling, 68 (28%) matched unrelated, and 40 (17%) mismatched unrelated donor transplants. The median post-transplant ferritin value among 1-year survivors of allogeneic transplant was 628 ng/ml (95% CI 17, 5010), with 93 (39%) above 1000 ng/ml and 40 (17%) above 2500 ng/ml. The median post-transplant ferritin levels varied by underlying hematologic disease (aplastic anemia = 1147, acute leukemia = 1067, MDS = 944, CLL = 297, CML = 219, lymphoma = 123, multiple myeloma = 90). The Kaplan-Meier projected 5-year survival rate was 76% for the cohort that had survived one year and had available ferritin values. Fifty late deaths have occurred; causes of late death were disease relapse (n=37, 74%), GVHD (n=7, 14%), infection (n=4, 8%), cardiac (n=1, 2%) and second malignancy (n=1, 2%). The 1-year post-transplant serum ferritin value was a significant predictor of long term survival. Using a cut-off ferritin value of 1000 ng/ml, the 5-year projected survivals were 85% (95 CI 75%-91%) and 64% (95% CI 52–73%) for the low and high ferritin cohorts respectively (Figure, log-rank p<0.001), with a hazard ratio of 3.5 (95% CI 2–6.4, p<0.001). Similarly a serum ferritin value >2500 ng/ml was associated with inferior survival (HR 2.97, p<0.001). Underlying hematologic disease also correlated with 5-year projected survival including 70%, 83%, and 89% for acute leukemia/MDS, lymphoma/myeloma/CLL, and aplastic anemia/CML groupings, respectively (log-rank p<0.01 for leukemia/MDS vs other groupings). Patients receiving bone marrow grafts did better than those receiving peripheral blood stem cells (HR = 2.2; p = 0.03). Age, gender, donor type (sibling, matched unrelated, mismatch unrelated) and intensity of regimen (ablative vs. non-myeloablative) were not predictive of inferior survival in univariate analysis. In the multivariate Cox-regression analysis, elevated post-transplant ferritin >1000 ng/ml (HR 3.3, 95%CI 1.6–6.1; p<0.001) and diagnosis of acute leukemia/MDS (HR 4.5, 95%CI 1.1–18.7; p=0.04) remained independent predictors of inferior survival, even when adjusted for age, gender, type of graft, donor type, and intensity of conditioning regimen. Relapse deaths (25% vs. 9%; p<0.001) and GVHD deaths (6% vs 0.6%; p=0.03) were more common in the high ferritin cohort.
Among patients who have survived one-year following allogeneic transplantation, a post-transplant serum ferritin value greater than 1000 ng/ml is a predictor of inferior long-term outcomes. To our knowledge this is the first report on the importance of late monitoring of serum ferritin, but it is in agreement with prior studies suggesting a pre-transplant ferritin value is a predictor of outcomes. Prospective studies attempting to modify outcomes by reducing post-transplant iron overload states are needed.
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No relevant conflicts of interest to declare.
3D Printing in Space National Research Council; Division on Engineering and Physical Sciences; National Materials and Manufacturing Board ...
09/2014
eBook
Odprti dostop
Additive manufacturing has the potential to positively affect human spaceflight operations by enabling the in-orbit manufacture of replacement parts and tools, which could reduce existing logistics ...requirements for the International Space Station and future long-duration human space missions. The benefits of in-space additive manufacturing for robotic spacecraft are far less clear, although this rapidly advancing technology can also potentially enable space-based construction of large structures and, perhaps someday, substantially in the future, entire spacecraft. Additive manufacturing can also help to reimagine a new space architecture that is not constrained by the design and manufacturing confines of gravity, current manufacturing processes, and launch-related structural stresses.
The specific benefits and potential scope of additive manufacturing remain undetermined. The realities of what can be accomplished today, using this technology on the ground, demonstrate the substantial gaps between the vision for additive manufacturing in space and the limitations of the technology and the progress that has to be made to develop it for space use.
3D Printing in Space evaluates the prospects of in-space additive manufacturing. This report examines the various technologies available and currently in development, and considers the possible impacts for crewed space operations and robotic spacecraft operations. Ground-based additive manufacturing is being rapidly developed by industry, and 3D Printing in Space discusses government-industry investments in technology development. According to this report, the International Space Station provides an excellent opportunity for both civilian and military research on additive manufacturing technology. Additive manufacturing presents potential opportunities, both as a tool in a broad toolkit of options for space-based activities and as a potential paradigm-changing approach to designing hardware for in-space activities. This report makes recommendations for future research, suggests objectives for an additive manufacturing roadmap, and envisions opportunities for cooperation and joint development.
The numbers of frail older persons using emergency departments are already considerable and will continue to increase over time. There are a number of issues related to the assessment and care of ...older patients that are significantly different to other patient groups. The traditional emergency department (ED) model focusing on rapid triage, treatment and throughput does not meet the needs of many older patients, who have complex presentations, and require comprehensive assessment and referral. In response to this, there are already a number of appropriate and innovative approaches to the care of the older patient demonstrated in the literature. Nurses have a crucial role in contributing to these approaches and in raising the profile of quality care of the older person. Some specific areas that ED nurses can focus on include a more comprehensive approach to assessment and discharge planning, improved communication with the patient and their personal carers, attention to basic nursing care, and making the physical environment safer and less stressful for the older patient. While developing collaborations with their aged care nursing colleagues is important, emergency nurses need to view care of the older person as a central part of their own core business.
One of our most distinguished economists, Sir Alan Peacock, also happens to be a nonagenarian.
As an academic and former civil servant, Peacock is well-situated to analyse the costs and benefits of ...retirement and the courses of action that we can take in anticipation of a lengthening lifespan.In trying to make sense of old age by writing of his later life and memoirs, he explores the Maxims of Francois, Duc de La Rochefoucauld, and views life's later stages and travails with a wry and clear-eyed detachment. Unafraid to grasp the realities of the decline of physical independence, he steers us through medical practice, bureaucracy and "healthspeak" as well as loss and bereavement.
His often light-hearted anecdotes reveal a serious point; that the ageing are assuming a growing responsibility for the aged. Opting to defy decrepitude seems the only sensible course of action.
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