BACKGROUND

Tagged magnetic resonance imaging (MRI) is the non-invasive golden standard to measure myocardial deformity. Tissue Doppler Imaging can be used to assess myocardial deformity, however, it has the limitation of angle-dependence. Our study aimed to compare left ventricular torsion and strains measured by velocity-vector imaging (VVI) using echocardiography (echo-VVI) and MRI (MRI-VVI), and to validate them against harmonic phase tagged MRI (HARP MRI).

METHODS

A total number of 34 subjects (14 normal and 20 patients) were evaluated. Apical and basal image of left ventricular short axis view were acquired for measurements of apical and basal rotation, circumferential and radial strain using both echo-VVI and MRI-VVI. An apical four-chamber view was obtained for measuring the distance between the apical and basal levels.

RESULTS

The correlations of segmental rotations, circumferential and radial strains were high between echo-VVI and HARP MRI, while the agreement of apical rotation was poor. Left ventricular torsion showed much better correlation and agreement between echo-VVI and HARP MRI than apical rotation: the coefficient was 0.97, P < 0.001. The correlation between MRI-VVI and HARP MRI in quantifying rotational parameters and strains was similar with echo-VVI and HARP MRI. Echo-VVI could discriminate normal and dysfunctional ventricles on either hypertensive or dilated cardiomyopathy.

CONCLUSIONS

The data from this study show that (1) it is feasible to quantify left ventricular torsion and myocardial strain using echo-VVI and MRI-VVI in normal subjects, patients with left ventricular global systolic dysfunction and segment systolic dysfunction; (2) the agreement among all mechanical parameters derived from echo-VVI, MRI-VVI, and HARP MRI remained with clinically acceptable ranges.

BACKGROUND

Emery-Dreifuss muscular dystrophy is a genetically heterogeneous form of muscular dystrophy. One form is inherited in an X-linked fashion and is secondary to mutations in the gene encoding the nuclear protein emerin. A more common variant is inherited in an autosomal dominant way (EDMD2) due to mutations affecting the nuclear lamina protein lamin A/C. Typical features of both conditions are relatively mild skeletal muscle weakness, but cardiac involvement develops almost invariably by adult age, including conduction defects, arrhythmias and cardiomyopathy. Thus, early detection of cardiac abnormalities may be important for planning early therapeutic intervention.

OBJECTIVE

In this study, we hypothesized that early myocardial dysfunction can be detected by tissue Doppler echocardiography and CMR in unselected patients with the autosomal dominant form of Emery-Dreifuss muscular dystrophy. This would suggest that fibrosis could be implicated in the pathogenesis of cardiac dysfunction in EDMD2.

METHODS

Eight consecutive patients with genetically proven EDMD2 without pacemakers were enrolled in the study and compared to eight age-matched controls. All patients and controls first underwent a comprehensive echocardiographic-Doppler examination, followed by measurement of mitral annular velocities using pulsed tissue Doppler. Color M-mode tissue images were recorded from the parasternal long axis projections to derive Myocardial Velocity Gradients (MVG). Subsequently, all subjects underwent cardiovascular magnetic resonance (CMR) imaging for function, intrinsic myocardial tissue contrast using T1 and T2 weighted spin echo (TSE) for fat deposition and extrinsic contrast (Gadolinium-DTPA late fibrosis imaging). Strain measurements, using harmonic phase imaging (HARP) tagging were also derived.

RESULTS

Cavity dimensions LV mass and fractional shortening were similar between patients and controls. The overall body mass index was less in patients than in controls (14.5 +/- 1.4 vs. 18.1 +/- 2.4 g/m2, p < 0.002). While systolic MVG were similar between groups, the early diastolic MVG was lower in patients than in controls (4 +/- 1.2 s-1 vs. 7.1 +/- 2.7, p < 0.02). On CMR, LA and LV, RV volumes were similar between patients and controls. CMR strain patterns, however, showed a significant reduction in inferior wall contractility in patients compared to controls (-0.06 +/- 0.02 vs -0.09 +/- 0.03, p < 0.05). No patient showed late gadolinium enhancement.

CONCLUSIONS

Patients with EDMD2 have abnormal left ventricular function prior to developing any cardiac symptoms. The absence of myocardial fibrosis, however, by CMR suggests that this functional abnormality may not be secondary to scarring but could precede it. Tissue Doppler echocardiography and CMR are sensitive methods of assessing the presence of myocardial dysfunction prior to the development of any cardiovascular symptoms.

Understanding the deformation of the tongue during human speech is important for head and neck surgeons and speech and language scientists. Tagged magnetic resonance (MR) imaging can be used to image 2D motion, and data from multiple image planes can be combined via post-processing to yield estimates of 3D motion. However, lacking boundary information, this approach suffers from inaccurate estimates near the tongue surface. This paper describes a method that combines two sources of information to yield improved estimation of 3D tongue motion. The method uses the harmonic phase (HARP) algorithm to extract motion from tags and diffeomorphic demons to provide surface deformation. It then uses an incompressible deformation estimation algorithm to incorporate both sources of displacement information to form an estimate of the 3D whole tongue motion. Experimental results show that use of combined information improves motion estimation near the tongue surface, a problem that has previously been reported as problematic in HARP analysis, while preserving accurate internal motion estimates. Results on both normal and abnormal tongue motions are shown.

This study explores the potential differences in comorbidity and course between primary generalized anxiety disorder (GAD), which develops before other anxiety disorders, and secondary GAD. As part of the Harvard/Brown Anxiety Research Project (HARP), a naturalistic, long-term, longitudinal study of 711 subjects from a variety of clinic settings with DSM III-R defined anxiety disorders, 210 subjects with GAD were identified. Of these, 78 (37%) had primary GAD, and 84 (40%) had secondary GAD; of the remainder, 28 (13%) had no other anxiety disorder and 20 (10%) developed GAD within a month of another anxiety disorder and were excluded from the analysis. All subjects were comorbid for at least one other anxiety disorder. Primary GAD subjects were more likely to be in episode at intake (90% vs. 77%, P = .04) and less likely than secondary GAD subjects to have current or past agoraphobia without panic disorder (3% vs. 11%, P = .04), social phobia (19% v. 52%, P = .001), simple phobia (14% v. 30%, P = .02), or post traumatic stress disorder (5% vs. 20%, P = .01). Subjects with primary GAD were also less likely to have current or past alcohol use disorders (17% vs. 37%, P = .004) or major depressive disorder (60% vs. 76%, P = .03). There were no significant differences in either treatment approaches or remission rates for primary compared to secondary GAD. Whether GAD first occurs before or after another anxiety disorder, it is similar in terms of prevalence, treatment, and course. The only significant differences between primary and secondary GAD lie in the rates of comorbidity of both other anxiety disorders and non-anxiety disorders, including major depression and substance abuse. These results support the concept of GAD as a valid, separate and distinct entity, whether it occurs primarily or secondarily.

Although avalanche amorphous selenium (a-Se) is a very promising photoconductor for a variety of imaging applications, it is currently restricted to applications with electron beam readout in vacuum pick-up tube called a High-gain Avalanche Rushing Photoconductor (HARP). The electron beam readout is compatible with high definition television (HDTV) applications, but for use in solid-state medical imaging devices it should be replaced by an electronic readout with a two-dimensional array of metal pixel electrodes. However, due to the high electric field required for avalanche multiplication, it is a technological challenge to avoid possible dielectric breakdown at the edges, where electric field experiences local enhancement. It has been shown recently that this problem can be overcome by the use of a Resistive Interface Layer (RIL) deposited between a-Se and the metal electrode, however, at that time, at a sacrifice in transport properties.Here we show that optimization of RIL deposition technique allows for electroded avalanche a-Se with transport properties and time performance previously not achievable with any other a-Se structures. We have demonstrated this by detailed analysis of transport properties performed by Time-of-Flight (TOF) technique. Our results showed that a stable gain of 200 is reached at 104 V/μm for a 15-μm thick a-Se layer, which is the maximum theoretical gain for this thickness. We conclude that RIL is an enabling technology for practical implementation of solid-state avalanche a-Se image sensors.

In 2010, approximately 500,000 Canadians suffered from a dementia-related illness. The number of sufferers is estimated to double in about 25 years. Due to this growing demographic, dementia (most frequently caused by Alzheimer's disease) will increasingly have a significant impact on our aging community and their caregivers. Dementia is associated with challenging behaviours such as agitation, wandering, and aggression. Care providers must find innovative strategies that facilitate the quality of life for this population; moreover, such strategies must value the individual person. Social commitment robots - designed specifically with communication and therapeutic purposes - provide one means towards attaining this goal. This paper describes a study in which Paro (a robotic baby harp seal) was used as part of a summer training program for students. Preliminary conclusions suggest that the integration of social commitment robots may be clinically valuable for older, agitated persons living with dementia in long-term care settings.

Half of the world's forest is in boreal and sub-boreal ecozones, containing large carbon stores and fluxes. Carbon lost from headwater streams in these forests is underestimated. We apply a simple stable carbon isotope idea for quantifying the CO2 loss from these small streams; it is based only on in-stream samples and integrates over a significant distance upstream. We demonstrate that conventional methods of determining CO2 loss from streams necessarily underestimate the CO2 loss with results from two catchments. Dissolved carbon export from headwater catchments is similar to CO2 loss from stream surfaces. Most of the CO2 originating in high CO2 groundwaters has been lost before typical in-stream sampling occurs. In the Harp Lake catchment in Canada, headwater streams account for 10% of catchment net CO2 uptake. In the Krycklan catchment in Sweden, this more than doubles the CO2 loss from the catchment. Thus, even when corrected for aquatic CO2 loss measured by conventional methods, boreal and sub-boreal forest carbon budgets currently overestimate carbon sequestration on the landscape.

Heteroaromatic polycycle (HARP) compounds are a novel class of small (M(w), 600 to 650) DNA-binding antibacterials. HARP compounds exhibit a novel mechanism of action by preferentially binding to AT-rich sites commonly found in bacterial promoters and replication origins. Noncovalent binding in the minor groove of DNA results in inhibition of DNA replication and DNA-dependent RNA transcription and subsequent bacterial growth. HARP compounds have previously been shown to have potent in vitro activities against a broad spectrum of gram-positive organisms. The present report describes the extensive profiling of the in vitro and in vivo pharmacology of HARP antibacterials. The efficacies of representative compounds (GSQ-2287, GSQ-10547, and GSQ-11203), which exhibited good MIC activity, were tested in murine lethal peritonitis and neutropenic thigh infection models following intravenous (i.v.) administration. All compounds were efficacious in vivo, with potencies generally correlating with MICs. GSQ-10547 was the most potent compound in vitro and in vivo, with a 50% effective dose in the murine lethal peritonitis model of 7 mg/kg of body weight against methicillin-sensitive Staphylococcus aureus (MSSA) and 13 mg/kg against methicillin-resistant S. aureus (MRSA). In the neutropenic mouse thigh infection model, GSQ-11203 reduced the bacterial load (MRSA and MSSA) 2 log units following administration of a 25-mg/kg i.v. dose. In a murine lung infection model, treatment with GSQ-10547 at a dose of 50 mg/kg resulted in 100% survival. In addition to determination of efficacy in animals, the pharmacokinetic and tissue disposition profiles in animals following administration of an i.v. dose were determined. The compounds were advanced into broad safety screening studies, including screening for safety pharmacology, genotoxicity, and rodent toxicity. The results support further development of this novel class of antibiotics.

Heparin affin regulatory peptide (HARP), also named pleiotropin, is a secreted polypeptide that belongs to a new family of heparin-binding growth/differentiation factors. In this study, we investigated the expression and distribution of HARP mRNA and protein in rat uterus. Semi-quantitative reverse transcriptase PCR experiments showed variations in HARP mRNA levels throughout the estrous cycle, with a maximum during diestrus, pointing to hormonal regulation of HARP mRNA expression. Uterine expression of HARP mRNA was studied in ovariectomized animals treated with 17 beta-estradiol, progesterone alone or progesterone and RU486. In these experiments, progesterone upregulated HARP mRNA expression. Induction was observed 6 h after progesterone injection and was inhibited by RU486 treatment. In contrast, after 17 beta-estradiol injection, a slight decrease in HARP mRNA expression was observed. In situ hybridization studies with digoxigenin-labeled DNA probe revealed that HARP mRNA was present in smooth muscle cells of both myometrium and blood vessels and also in endothelial cells from endometrium. Immunohistochemical studies showed that HARP expression was not limited to cells that expressed HARP mRNA, but also occurred in both the luminal and glandular epithelium even though its transcript was never detected. We conclude that HARP may mediate the effects of progesterone on the homeostasis and vascularization of uterine tissue.

OBJECTIVE

To present the first experience with a 3-port technique for retroperitoneoscopic (HARP) radical nephrectomy, radical nephroureterectomy, and total and live donor nephrectomy. We believe that the retroperitoneoscopic (RP) approach to nephrectomy is advantageous, as it avoids mobilization of intraperitoneal organs and provides direct access to the renal artery. Nonetheless, this approach is not as popular as the transperitoneal approach, likely because of the steeper learning curve. We believe that hand-assistance reduces the learning curve because of the tactile feedback and similarity to open surgery.

METHODS

Over a 4-year period, 133 HARP nephrectomies were performed, including 92 radical nephrectomies, 19 radical nephroureterectomies, 12 total nephrectomies, and 10 live donor nephrectomies. Mean patient age was 62 years and mean body mass index was 30; 42% of patients had abdominal scars. Our technique uses a 7-cm muscle-sparing Gibson incision for the hand-port with 2 endoscopic ports.

RESULTS

Mean operative time, including ureterectomy, was 109 minutes, with a mean operative blood loss of 167 mL. Average hospitalization was 3.8 days. Two cases (1.5%) required open conversion. The complication rate was limited to 3.8% for blood transfusion, 3.8% for cardiac issues, 1.5% for pulmonary embolism, 2.3% for wound infection, and 1.5% for urinary retention.

CONCLUSIONS

Based on our results, we conclude that HARP nephrectomy is safe and effective and can be expeditiously performed. It is a versatile approach that is applicable for both neoplastic and non-neoplastic indications. In addition, HARP provides a minimally invasive alternative to open conversion in difficult cases of simple nephrectomy.

A middle-aged man with lung cancer breathes more easily and reduces his need for pain medication after participating in music-focused relaxation. An 8-year-old boy with cancer writes songs and records a CD for his family. An elderly woman in the final stages of Alzheimer's who is no longer able to speak sings a few words of her favorite lullaby to her adult daughter. A much-loved grandmother dies peacefully as her family sings her favorite spiritual songs to the accompaniment of a music therapist's folk harp. These illustrations demonstrate the role that music therapy plays in attending to the physical, emotional, and spiritual needs of hospice and palliative care patients and families while respecting their dignity and celebrating their lives.

An indirect flat panel imager (FPI) with programmable avalanche gain and field emitter array (FEA) readout is being investigated for low-dose and high resolution x-ray imaging. It is made by optically coupling a structured x-ray scintillator, e.g., thallium (Tl) doped cesium iodide (CsI), to an amorphous selenium (a-Se) avalanche photoconductor called high-gain avalanche rushing amorphous photoconductor (HARP). The charge image created by the scintillator/HARP (SHARP) combination is read out by the electron beams emitted from the FEA. The proposed detector is called scintillator avalanche photoconductor with high resolution emitter readout (SAPHIRE). The programmable avalanche gain of HARP can improve the low dose performance of indirect FPI while the FEA can be made with pixel sizes down to 50 microm. Because of the avalanche gain, a high resolution type of CsI (Tl), which has not been widely used in indirect FPI due to its lower light output, can be used to improve the high spatial frequency performance. The purpose of the present article is to investigate the factors affecting the spatial resolution of SAPHIRE. Since the resolution performance of the SHARP combination has been well studied, the focus of the present work is on the inherent resolution of the FEA readout method. The lateral spread of the electron beam emitted from a 50 microm x 50 microm pixel FEA was investigated with two different electron-optical designs: mesh-electrode-only and electrostatic focusing. Our results showed that electrostatic focusing can limit the lateral spread of electron beams to within the pixel size of down to 50 microm. Since electrostatic focusing is essentially independent of signal intensity, it will provide excellent spatial uniformity.

Heparin affin regulatory peptide (HARP) is a growth factor displaying high affinity for heparin. It is present in the extracellular matrix of many tissues, interacting with heparan sulfate and dermatan/chondroitin sulfate glycosaminoglycans. We have previously shown that HARP is implicated in the control of angiogenesis and its effects are mimicked, at least in part, by synthetic peptides that correspond to its N and C termini. In the present work, we show that HARP is cleaved by plasmin, leading to the production of five peptides that correspond to distinct domains of the molecule. Heparin, heparan sulfate and dermatan sulfate, at various HARP to glycosaminoglycan ratios, partially protect HARP from plasmin degradation. The molecules with higher affinity to HARP are the more protective, heparin being the most efficient. The peptides that are produced from cleavage of HARP by plasmin, affect in vivo and in vitro angiogenesis and modulate the angiogenic activity of vascular endothelial growth factor on human umbilical vein endothelial cells. Similar results were obtained in vitro with recombinant HARP peptides, identical to the peptides generated after treatment of HARP with plasmin. These results suggest that different regions of HARP may induce or inhibit angiogenesis.

Heparin affin regulatory peptide (HARP), also called pleiotrophin (PTN), is a secreted polypeptide which binds to heparin and plays a key role in cellular growth and differentiation. In order to assess the determinants potentially important to its biological activity, we tested the ability of HARP to oligomerize, a process involved in mitogenic activity of the heparin-binding fibroblast growth factor. Using dissuccinimidyl suberate cross-linking experiments and affinity chromatography, we report that human HARP forms noncovalent dimers. Dimerization is dependent on the presence of heparin or other sulfated glycosaminoglycans, as chlorate treatment of cells inhibits this process. In vitro, different glycosaminoglycans, such as dermatan sulfate and chondroitin sulfate-C, also induce a dimer assembly of HARP. The relevance of this process was supported by experiments demonstrating that HARP is secreted as a dimer in conditioned medium of NIH-3T3 cells that overexpressed this growth factor and is also associated to the cell surface or to the extracellular matrix.

Heparin affin regulatory peptide (HARP) also named pleiotrophin (PTN) is a polypeptide that belongs to a family of heparin-binding molecules. HARP displays mitogenic activity for a wide variety of cells, including fibroblast, endothelial and epithelial cells. This study reports, to our knowledge for the first time that HARP induced the stimulation of triated thymidine incorporation in quiescent human peripheral blood mononuclear cells in a dose-dependant manner, measured after 7 days of culture. Maximal stimulation was observed at picomolar concentration with ED50 corresponding to the half maximum effect at 50 pM. In contrast, midkine (MK), a related heparin-binding growth/differentiation factor, with more than 50% amino acid sequence homology with HARP was ineffective. These results suggest that HARP could be considered as a new cytokine involved inthe growth regulation of cell mediated immunity.

Harp seals (Pagophilus groenlandicus) have evolved life history strategies to exploit seasonal sea ice as a breeding platform. As such, individuals are prepared to deal with fluctuations in the quantity and quality of ice in their breeding areas. It remains unclear, however, how shifts in climate may affect seal populations. The present study assesses the effects of climate change on harp seals through three linked analyses. First, we tested the effects of short-term climate variability on young-of-the year harp seal mortality using a linear regression of sea ice cover in the Gulf of St. Lawrence against stranding rates of dead harp seals in the region during 1992 to 2010. A similar regression of stranding rates and North Atlantic Oscillation (NAO) index values was also conducted. These analyses revealed negative correlations between both ice cover and NAO conditions and seal mortality, indicating that lighter ice cover and lower NAO values result in higher mortality. A retrospective cross-correlation analysis of NAO conditions and sea ice cover from 1978 to 2011 revealed that NAO-related changes in sea ice may have contributed to the depletion of seals on the east coast of Canada during 1950 to 1972, and to their recovery during 1973 to 2000. This historical retrospective also reveals opposite links between neonatal mortality in harp seals in the Northeast Atlantic and NAO phase. Finally, an assessment of the long-term trends in sea ice cover in the breeding regions of harp seals across the entire North Atlantic during 1979 through 2011 using multiple linear regression models and mixed effects linear regression models revealed that sea ice cover in all harp seal breeding regions has been declining by as much as 6 percent per decade over the time series of available satellite data.

Between 1976 and 1978, 248 harp seals were sampled from 5 locations in the Northwest Atlantic and Arctic for organochlorine (OC) residue analysis in tissue. Blood, kidney, brain, muscle and blubber samples were analysed for PCB, DDT, dieldrin, hexachlorobenzene (HCB), and heptachlor epoxide. Levels were generally greatest in blubber tissue. Overall, mean levels of DDT and PCB were greater than those of other OC. A barrier prevented OC compounds from accumulating in the brain to the level one might expect in lipid tissues. Positive correlations were found between 1: DDT and PCB, 2: DDT and dieldrin, and 3: PCB and deildrin. Male harp seals bioaccumulated DDT, PCB, heptachlor epoxide and dieldrin with age. As a group, adult males sampled in the Gulf of St. Lawrence carried the highest concentrations of all OC, except that chlordane did not appear to bioaccumulate and levels of hexachlorobenzene were minimal. Females generally ceased exhibiting significant bioaccumulation once breeding age was reached, due to transplacental and transmammary residue transfer of OC from mother to pup. There were some significant differences in OC levels between locations with DDT: Gulf greater than Front; PCB: Gulf greater than Front; dieldrin: Gulf greater than Front; heptachlor epoxide: Front greater than Gulf. No significant differences were found, however, when northern locations (Grise Fiord, Northwest Greenland, Pangnirtung) were compared to southern (Gulf, Front) on a group basis. The latter is not surprising in view of the harp seals extensive cyclical annual migration between the southern breeding grounds and the High Arctic.

Cysts of Giardia sp. were detected in feces from the rectum of 20 of 74 pinnipeds examined from the eastern coast of Canada in 1997 and 1998 using a monoclonal antibody technique. Infected pinnipeds included 15 adult harp seals (Phoca groenlandica), four adult grey seals (Halichoerus grypus), and one juvenile harbor seal (Phoca vitulina). Cysts were not detected in 15 seal pups <1-yr-old. The highest prevalence (50%) occurred in adult harp seals collected near the Magdalen Islands in the Gulf of St. Lawrence. The overall prevalence of Giardia sp. in grey and harbor seals, excluding pups, from the Gulf and St. Lawrence estuary was 23%. Feces from 11 beluga (Delphinapterus leucas) and one northern bottle-nosed whale (Hyperoodon ampullatus) stranded in the St. Lawrence estuary were negative for Giardia sp. cysts. The significance of Giardia sp. in marine mammals, shown here for the first time in eastern coastal Canada, is unknown.

BACKGROUND

Pleiotrophin, also known as HARP (Heparin Affin Regulatory Peptide) is a growth factor expressed in various tissues and cell lines. Pleiotrophin participates in multiple biological actions including the induction of cellular proliferation, migration and angiogenesis, and is involved in carcinogenesis. Recently, we identified and characterized several pleiotrophin proteolytic fragments with biological activities similar or opposite to that of pleiotrophin. Here, we investigated the biological actions of P(122-131), a synthetic peptide corresponding to the carboxy terminal region of this growth factor.

RESULTS

Our results show that P(122-131) inhibits in vitro adhesion, anchorage-independent proliferation, and migration of DU145 and LNCaP cells, which express pleiotrophin and its receptor RPTPβ/ζ. In addition, P(122-131) inhibits angiogenesis in vivo, as determined by the chicken embryo CAM assay. Investigation of the transduction mechanisms revealed that P(122-131) reduces the phosphorylation levels of Src, Pten, Fak, and Erk1/2. Finally, P(122-131) not only interacts with RPTPβ/ζ, but also interferes with other pleiotrophin receptors, as demonstrated by selective knockdown of pleiotrophin or RPTPβ/ζ expression with the RNAi technology.

CONCLUSIONS

In conclusion, our results demonstrate that P(122-131) inhibits biological activities that are related to the induction of a transformed phenotype in PCa cells, by interacing with RPTPβ/ζ and interfering with other pleiotrophin receptors. Cumulatively, these results indicate that P(122-131) may be a potential anticancer agent, and they warrant further study of this peptide.

The current research (1) examines empirical evidence to substantiate the relationship between substance choice and chronology of onset of anxiety and substance use disorders, and (2) provides information on the specificity of substance choice among anxiety disorders. A study group of 181 subjects in the Harvard Anxiety Research Project (HARP) who had a history of substance use disorder were the focus of this examination. Subjects whose anxiety disorder had an onset before their substance use disorder (primary anxiety) were compared with those whose substance use preceded onset of an anxiety disorder (secondary anxiety) for differences in distribution of subjects among categories of substance of abuse. Primary and secondary anxiety groups do not have different ages of onset for substance use disorder, nor was there greater likelihood for choosing alcohol for any of the anxiety disorders. However, there is a decreased risk of alcohol use in the small group of generalized anxiety subjects and an increased risk of opioid use in the small group of posttraumatic stress disorder subjects. There was no indirect support for the self-medication hypothesis. Neither age of onset data, specific substance association, nor proximal diagnosis association support a simple interaction. The strongest finding supported an "avoidance" of CNS stimulants.

Heparin-affin regulatory peptide (HARP) and Midkine (MK) belong to a family of growth/differentiation factors that have a high affinity for heparin. The involvement of these molecules in various proliferative diseases prompted us to develop an assay for measuring the concentrations of these factors in biological fluids and culture media. This report describes an immunoassay that uses only commercially available materials, based on the high affinity of certain molecules for heparin. It consists of adsorbing heparin-BSA covalent complexes to microtiter plate wells and to quantify the heparin bound HARP or MK by using appropriate antibody. The method is specific and measures concentrations ranging from 40-1200 pg/mL HARP and from 25-1200 pg/mL MK and various parameters are investigated. The within-assay coefficient of variation was less than 5% for both assays. The method was checked by measuring the concentrations of these growth factors in the sera of healthy humans and in patients with cancer. As previously reported, we confirmed that the serum concentrations of MK are higher in patients with tumours (n = 139) than in controls (n = 19). The synthesis of HARP and MK by various cells in culture was also analysed.

Engineered muscle tissues used as transplant tissues in regenerative medicine should have a three-dimensional and cell-dense structure like native tissue. For fabricating a 3D cell-dense muscle tissue from myoblasts, we proposed the electrospun type I collagen microfiber scaffold of the string-shape like a harp. The microfibers were oriented in the same direction to allow the myoblasts to align, and were strung at low density with micrometer intervals to create space for the cells to occupy. To realize this shape of the scaffold, we employed in situ cross-linking during electrospinning process for the first time to collagen fibers. The collagen microfibers in situ cross-linked with glutaraldehyde stably existed in the aqueous media and completely retained the original shape to save the spaces between the fibers for over 14 days. On the contrary, the conventional cross-linking method by exposure to a glutaraldehyde aqueous solution vapor partially dissolved and damaged the fiber to lose a low-density shape of the scaffold. Myoblasts could penetrate into the interior of the in situ cross-linked string-shaped scaffold and form the cell-dense muscle tissues. Histochemical analysis showed the total area occupied by the cells in the cross section of the tissue was approximately 73 %. Furthermore, the resulting muscle tissue fabricated from primary myoblasts showed typical sarcomeric cross-striations and the entire tissue continuously pulsated by autonomous contraction. Together with the in situ cross-linking, the string-shaped scaffold provides an efficient methodology to fabricate a cell-dense 3D muscle tissue, which could be applied in regenerative medicine in future.

The demographic history of Greenland is characterized by recurrent migrations and extinctions since the first humans arrived 4,500 years ago. Our current understanding of these extinct cultures relies primarily on preserved fossils found in their archaeological deposits, which hold valuable information on past subsistence practices. However, some exploited taxa, though economically important, comprise only a small fraction of these sub-fossil assemblages. Here we reconstruct a comprehensive record of past subsistence economies in Greenland by sequencing ancient DNA from four well-described midden deposits. Our results confirm that the species found in the fossil record, like harp seal and ringed seal, were a vital part of Inuit subsistence, but also add a new dimension with evidence that caribou, walrus and whale species played a more prominent role for the survival of Paleo-Inuit cultures than previously reported. Most notably, we report evidence of bowhead whale exploitation by the Saqqaq culture 4,000 years ago.